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Kjaergaard AD, Vaag AA, Jensen VH, Olsen MH, Højlund K, Vestergaard P, Hansen T, Thomsen RW, Jessen N. YKL-40 and risk of incident cancer in early type 2 diabetes: a Danish cohort study. Br J Cancer 2025; 132:1019-1026. [PMID: 40188292 PMCID: PMC12119867 DOI: 10.1038/s41416-025-02996-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 03/06/2025] [Accepted: 03/21/2025] [Indexed: 04/07/2025] Open
Abstract
BACKGROUND We examined the association of serum YKL-40, an inflammatory biomarker, with incident cancer risk in early type 2 diabetes. METHODS A cohort of 11,346 individuals newly diagnosed with type 2 diabetes was followed for up to 14 years. YKL-40 levels (n = 9010) were categorised into five percentiles (0-33%, 34-66%, 67-90%, 91-95%, and 96-100%), and baseline YKL-40 and CRP (n = 9644) were analyzed continuously (per 1 SD log increment) for comparison. Cox regression models assessed associations with obesity-related, gastrointestinal, liver, pancreatic, colorectal, bladder and lung cancers, as well as cancers of reproductive organs. RESULTS Adjusted HRs (95% CIs) for the highest versus lowest YKL-40 category were 2.4 (1.6-3.7) for obesity-related, 2.6 (1.7-4.1) for gastrointestinal, 44.2 (12.8-153.4) for liver, and 4.2 (1.3-14.1) for bladder cancers. No associations were found for other cancers. YKL-40 and CRP had similar prognostic abilities for obesity-related and gastrointestinal cancers, but YKL-40 outperformed CRP for liver and bladder cancers. Conversely, CRP was a stronger predictor for lung, colorectal, and ovarian cancers. DISCUSSION YKL-40 was associated with the risks of liver and bladder cancers, clearly outperforming CRP for these cancers. This suggests distinct prognostic roles for YKL-40 and CRP, and highlights YKL-40 as a promising biomarker for liver cancer.
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Affiliation(s)
- Alisa D Kjaergaard
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
| | - Allan A Vaag
- Steno Diabetes Center Copenhagen, Copenhagen University Hospital, Herlev, Denmark
- Lund University Diabetes Center, Lund University, Lund, Sweden and Department of Endocrinology, Skåne University Hospital, Malmö, Sweden
| | - Verena H Jensen
- Steno Diabetes Center Copenhagen, Copenhagen University Hospital, Herlev, Denmark
| | - Michael H Olsen
- Department of Internal Medicine and Steno Diabetes Center Zealand, Holbæk Hospital, Holbæk, Denmark
| | - Kurt Højlund
- Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark
| | - Peter Vestergaard
- Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark
| | - Torben Hansen
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Reimar W Thomsen
- Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark
| | - Niels Jessen
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
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Kasapoglu Dilek E, Tekin K, Cankurtaran V, Dogan S, Dirican E. The relationship between different stages of diabetic retinopathy and levels of YKL-40 in aqueous humour and serum. Clin Exp Optom 2025:1-6. [PMID: 39899896 DOI: 10.1080/08164622.2025.2461233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 12/18/2024] [Accepted: 01/27/2025] [Indexed: 02/05/2025] Open
Abstract
CLINICAL RELEVANCE Since inflammation plays an important role in the pathogenesis of diabetic retinopathy, serum biomarkers and retinal imaging aimed at evaluating the presence of inflammation have emerged as useful tools to monitor the appearance and progression of diabetic retinopathy. BACKGROUND This study aims to investigate the value of YKL-40 levels in patients with diabetes mellitus with different stages of diabetic retinopathy and without diabetic retinopathy, and to compare those findings with results from healthy individuals without diabetes mellitus. METHODS This prospective cross-sectional study included 67 diabetic patients with or without diabetic retinopathy who underwent cataract surgery and 23 patients (control group) having no ocular and systemic disease other than senile cataract. Participants with diabetes mellitus were separated into three subgroups: the first group consisted of 26 patients without diabetic retinopathy, the second group included 21 patients with non-proliferative diabetic retinopathy and the third group included 20 patients with proliferative diabetic retinopathy. Serum and aqueous humour YKL-40 levels were analysed and compared between the groups. RESULTS The mean serum (p < 0.001) and aqueous humour (p < 0.001) YKL-40 levels were statistically significantly lower in control subjects compared to patients with diabetes mellitus. The aqueous humour YKL-40 levels showed statistically significant elevations with the progression of diabetic retinopathy. Duration of diabetes mellitus was significantly correlated with aqueous humour YKL-40 levels (p = 0.001, r = 0.384). CONCLUSION Both serum and aqueous humour YKL-40 levels are higher in patients with diabetes mellitus compared to healthy subjects. Levels of YKL-40 in aqueous humour increase with the progression of diabetic retinopathy.
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Affiliation(s)
| | - Kemal Tekin
- Department of Ophthalmology, Ulucanlar Eye Training and Research Hospital, Ankara, Turkey
| | | | - Serdar Dogan
- Department of Biochemistry, Mustafa Kemal University, Hatay, Turkey
| | - Emre Dirican
- Department of Biostatistics, Mustafa Kemal University, Hatay, Turkey
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Kjaergaard AD, Vaag A, Jensen VH, Olsen MH, Højlund K, Vestergaard P, Hansen T, Thomsen RW, Jessen N. YKL-40, cardiovascular events, and mortality in individuals recently diagnosed with type 2 diabetes: A Danish cohort study. Diabetes Res Clin Pract 2025; 219:111970. [PMID: 39719182 DOI: 10.1016/j.diabres.2024.111970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Revised: 12/16/2024] [Accepted: 12/17/2024] [Indexed: 12/26/2024]
Abstract
AIMS We investigated the association of the inflammatory biomarker YKL-40 with cardiovascular events (CVEs) and mortality in individuals with type 2 diabetes. METHODS We followed 11,346 individuals recently diagnosed with type 2 diabetes for up to 14 years. Baseline YKL-40 levels (measured in 9,010 individuals) were grouped into percentiles (0-33 %, 34-66 %, 67-90 %, and 91-100 %) and analyzed continuously (per 1 SD log increment), with comparisons to CRP (measured in 9,644 individuals). Cox regression assessed associations with atrial fibrillation (AF), ischemic stroke (IS), venous thromboembolism (VTE), myocardial infarction (MI), heart failure (HF), peripheral artery disease (PAD), and all-cause, cardiovascular, and cancer mortality. RESULTS Adjusted HRs (95% CIs) for the highest (91-100%) versus the lowest (0-33%) YKL-40 percentile category were 1.31 (1.04-1.66) for AF, 1.43 (0.98-2.07) for IS, 1.07 (0.65-1.76) VTE, 0.88 (0.52-1.48) for MI, 1.66 (1.19-2.31) for HF, 1.66 (1.12-2.48) for PAD, and 2.18 (1.85-2.56) for all-cause, 1.64 (1.07-2.50) for cardiovascular, and 2.73 (2.05-3.63) for cancer mortality. Each 1 SD log increase in YKL-40 and CRP levels similarly increased CVE risks, with CRP being superior for MI and cardiovascular mortality. CONCLUSIONS YKL-40 is a prognostic biomarker for most CVEs, and even more so for all-cause mortality, primarily driven by cancer-related causes.
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Affiliation(s)
- Alisa D Kjaergaard
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
| | - Allan Vaag
- Steno Diabetes Center Copenhagen, Copenhagen University Hospital, Herlev, Denmark
| | - Verena H Jensen
- Steno Diabetes Center Copenhagen, Copenhagen University Hospital, Herlev, Denmark
| | - Michael H Olsen
- Department of Internal Medicine and Steno Diabetes Center Zealand, Holbæk Hospital, Holbæk, Denmark
| | - Kurt Højlund
- Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark
| | - Peter Vestergaard
- Steno Diabetes Center North Denmark, Aalborg University Hospital, Aalborg, Denmark
| | - Torben Hansen
- Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Reimar W Thomsen
- Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark
| | - Niels Jessen
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
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Chou HH, Teng MS, Juang JMJ, Chiang FT, Tzeng IS, Wu S, Ko YL. Circulating YKL-40 levels but not CHI3L1 or TRIB1 gene variants predict long-term outcomes in patients with angiographically confirmed multivessel coronary artery disease. Sci Rep 2024; 14:29416. [PMID: 39592699 PMCID: PMC11599938 DOI: 10.1038/s41598-024-81190-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 11/25/2024] [Indexed: 11/28/2024] Open
Abstract
YKL-40 is significantly associated with the prevalence and severity of coronary artery disease (CAD). YKL-40 levels are significantly associated with variations in the CHI3L1 and TRIB1 genes. We investigated candidate genes for YKL-40 levels and evaluated the prognostic value of this biomarker and corresponding variants for long-term outcomes in patients with CAD. We included 4664 and 521 participants from the Taiwan Biobank (TWB) and CAD cohorts, respectively. Candidate variants for circulating YKL-40 levels were investigated using genome-wide association study (GWAS) data from the TWB cohort, and the results were validated in the CAD cohort. The primary endpoint was all-cause mortality. The secondary endpoint was major adverse cardiac events (MACEs), which included the composite endpoints of all-cause mortality, nonfatal acute coronary syndrome, hospitalization for heart failure, and nonfatal stroke. According to the GWAS data from the TWB cohort, three CHI3L1 variants (rs4950928, rs10399931, and rs872129) and one TRIB1 variant (rs6982502) were independently associated with YKL-40 levels. These findings were validated in the CAD cohort. The combined CHI3L1 and TRIB1 weighted genetic risk scores (WGRSs) were not associated with the long-term outcomes (median follow-up period of 3.7 years) in patients with CAD. Conversely, patients with YKL-40 levels in the upper tertile had the highest rates of all-cause mortality and MACEs (log-rank p = 9.58 × 10-8 for all-cause mortality and 1.34 × 10-7 for MACEs). Furthermore, YKL-40 levels predicted poor clinical outcomes only in patients with multivessel CAD (log-rank p = 3.0 × 10-6 for all-cause mortality and 1.10 × 10-5 for MACEs) and not in patients with single-vessel CAD. This study revealed that YKL-40 levels but not the combined CHI3L1 and TRIB1 WGRSs were found to be independent predictors of poor clinical outcomes in patients with multivessel CAD.
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Affiliation(s)
- Hsin-Hua Chou
- Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 289 Jianguo Road, Xindian District, New Taipei City, 23142, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Ming-Sheng Teng
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
| | - Jyh-Ming Jimmy Juang
- Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Fu-Tien Chiang
- Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- College of Medicine, National Taiwan University, Taipei, Taiwan
- Division of Cardiology, Cardiovascular Center, Fu-Jen Catholic University Hospital, New Taipei City, Taiwan
| | - I-Shiang Tzeng
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
| | - Semon Wu
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan
- Department of Life Science, Chinese Culture University, Taipei, Taiwan
| | - Yu-Lin Ko
- Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 289 Jianguo Road, Xindian District, New Taipei City, 23142, Taiwan.
- School of Medicine, Tzu Chi University, Hualien, Taiwan.
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Rastegar-Moghaddam SH, Bigham M, Lombardi G, Mohammadipour A, Malvandi AM. MicroRNA-24 therapeutic potentials in infarction, stroke, and diabetic complications. Mol Biol Rep 2024; 51:1137. [PMID: 39520600 DOI: 10.1007/s11033-024-10089-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2024] [Accepted: 11/01/2024] [Indexed: 11/16/2024]
Abstract
The prevalence of cardiovascular events, stroke, and diabetes worldwide underscores the urgent need for effective and minimally invasive treatments. With nearly 20 million annual casualties attributed to cardiovascular diseases and an estimated 463 million people living with diabetes in 2022. Identifying promising therapeutic candidates is paramount. MicroRNAs, short nucleic acids involved in regulating gene expression, emerge as potential game-changers. Among these, microRNA-24 (miR-24), a hypoxia-sensitive player in endothelial vessels, has protective roles against diverse vascular complications. Following heart infarction and stroke, elevating miR-24 expression proves beneficial by mitigating oxidative stress, inflammation, and apoptosis while enhancing cell survival. It reduces cardiac fibrosis in heart disease, regulates aberrant angiogenesis in cerebral hemorrhagic strokes, and enhances the functionality of cardiomyocytes and brain neurons. In diabetic conditions, augmenting miR-24 expression mitigates complications. Further, being miR-24 also expressed by the skeletal muscle (i.e., myo-miR) in response to exercise, this miRNA may participate in the complex molecular network that systemically spreads the beneficial effects of physical exercise. This review provides a comprehensive vision of the molecular mechanisms underpinning the miR-24 protective effects, offering new insights into its therapeutic potential and proposing a novel avenue for medical intervention.
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Affiliation(s)
| | - Maryam Bigham
- Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Giovanni Lombardi
- Laboratory of Experimental Biochemistry & Molecular Biology, IRCCS Ospedale Galeazzi - Sant'Ambrogio, Milan, Italy
- Department of Athletics, Strength and Conditioning, Poznań University of Physical Education, Poznań, Poland
| | - Abbas Mohammadipour
- Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
- Applied Biomedical Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
- Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Amir Mohammad Malvandi
- Laboratory of Experimental Biochemistry & Molecular Biology, IRCCS Ospedale Galeazzi - Sant'Ambrogio, Milan, Italy.
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Qu Z, Lu Y, Ran Y, Xu D, Guo Z, Cheng M. Chitinase‑3 like‑protein‑1: A potential predictor of cardiovascular disease (Review). Mol Med Rep 2024; 30:176. [PMID: 39129301 PMCID: PMC11332322 DOI: 10.3892/mmr.2024.13300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Accepted: 07/23/2024] [Indexed: 08/13/2024] Open
Abstract
Chitinase‑3 like‑protein‑1 (CHI3L1), a glycoprotein belonging to the glycoside hydrolase family 18, binds to chitin; however, this protein lacks chitinase activity. Although CHI3L1 is not an enzyme capable of degrading chitin, it plays significant roles in abnormal glucose and lipid metabolism, indicating its involvement in metabolic disorders. In addition, CHI3L1 is considered a key player in inflammatory diseases, with clinical data suggesting its potential as a predictor of cardiovascular disease. CHI3L1 regulates the inflammatory response of various cell types, including macrophages, vascular smooth muscle cells and fibroblasts. In addition, CHI3L1 participates in vascular remodeling and fibrosis, contributing to the pathogenesis of cardiovascular disease. At present, research is focused on elucidating the role of CHI3L1 in cardiovascular disease. The present systematic review was conducted to comprehensively evaluate the effects of CHI3L1 on cardiovascular cells, and determine the potential implications in the occurrence and progression of cardiovascular disease. The present study may further the understanding of the involvement of CHI3L1 in cardiovascular pathology, demonstrating its potential as a therapeutic target or biomarker in the management of cardiovascular disease.
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Affiliation(s)
- Zhuojian Qu
- School of Basic Medicine Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Yirui Lu
- School of Basic Medicine Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Yutong Ran
- School of Basic Medicine Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Donghua Xu
- Central Laboratory of The First Affiliated Hospital, Shandong Second Medical University, Weifang, Shandong 261000, P.R. China
| | - Zhiliang Guo
- Department of Spine Surgery, The 80th Group Army Hospital of Chinese PLA, Weifang, Shandong 261021, P.R. China
| | - Min Cheng
- School of Basic Medicine Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
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7
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Zhang F, Han Y, Zheng L, Bao Z, Liu L, Li W. Association between chitinase-3-like protein 1 and metabolic-associated fatty liver disease in patients with type 2 diabetes mellitus. Ir J Med Sci 2024; 193:1843-1853. [PMID: 38520612 DOI: 10.1007/s11845-024-03671-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Accepted: 03/15/2024] [Indexed: 03/25/2024]
Abstract
BACKGROUND AND AIM Early identification of liver fibrosis is essential for the prognosis of metabolic-associated fatty liver disease (MAFLD), particularly in type 2 diabetes mellitus (T2DM) patients. Here, we explored the association of chitinase-3-like protein 1 (CHI3L1) and liver fibrosis in T2DM-MAFLD patients. METHODS Liver fibrosis was staged in T2DM-MAFLD patients, and a liver stiffness measurement (LSM) of ≥ 8 kPa was used to differentiate between non-significant (NSLF) and significant liver fibrosis (SLF) subgroups. The two subgroups were compared for serum CHI3L1 and other parameters. Linear correlation, logistic regression, and restricted cubic spline (RCS) analyses were performed to evaluate the association between CHI3L1 and liver fibrosis. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic accuracy of CHI3L1. RESULTS Among T2DM-MAFLD, SLF patients had higher CHI3L1 compared to NSLF patients. CHI3L1 was found to be positively correlated with LSM. Multivariate logistic regression analysis suggested that CHI3L1 may be a potential independent risk factor for SLF. Further stratified analysis indicated that the odds ratios of SLF in the high CHI3L1 group were higher than in the low CHI3L1 group in the subgroups. RCS analysis suggested an increasing trend in the incidence of significant fibrosis with the rising level of CHI3L1. The area under the ROC curve for detecting significant fibrosis was 0.749 (95% CI: 0.668-0.829). CONCLUSIONS Serum CHI3L1 demonstrates an association with significant liver fibrosis. High serum levels of CHI3L1 may indicate the existence of significant liver fibrosis in T2DM-MAFLD patients.
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Affiliation(s)
- Fan Zhang
- Department of Endocrinology, Changzhou Third People's Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China
- Department of Clinical Nutrition, Changzhou Third People's Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China
| | - Yan Han
- Department of Endocrinology, Changzhou Third People's Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China
- Department of Clinical Nutrition, Changzhou Third People's Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China
| | - Liming Zheng
- Clinical Laboratory, Changzhou Third People's Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China
| | - Zuowei Bao
- Department of Ultrasonography, Changzhou Third People's Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China
| | - Longgen Liu
- Department of Liver Diseases, Changzhou Third People's Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China.
| | - Wenjian Li
- Department of Urology, Changzhou Third People's Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China.
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Zhao H, Huang M, Jiang L. Potential Roles and Future Perspectives of Chitinase 3-like 1 in Macrophage Polarization and the Development of Diseases. Int J Mol Sci 2023; 24:16149. [PMID: 38003338 PMCID: PMC10671302 DOI: 10.3390/ijms242216149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 11/03/2023] [Accepted: 11/05/2023] [Indexed: 11/26/2023] Open
Abstract
Chitinase-3-like protein 1 (CHI3L1), a chitinase-like protein family member, is a secreted glycoprotein that mediates macrophage polarization, inflammation, apoptosis, angiogenesis, and carcinogenesis. Abnormal CHI3L1 expression has been associated with multiple metabolic and neurological disorders, including diabetes, atherosclerosis, and Alzheimer's disease. Aberrant CHI3L1 expression is also reportedly associated with tumor migration and metastasis, as well as contributions to immune escape, playing important roles in tumor progression. However, the physiological and pathophysiological roles of CHI3L1 in the development of metabolic and neurodegenerative diseases and cancer remain unclear. Understanding the polarization relationship between CHI3L1 and macrophages is crucial for disease progression. Recent research has uncovered the complex mechanisms of CHI3L1 in different diseases, highlighting its close association with macrophage functional polarization. In this article, we review recent findings regarding the various disease types and summarize the relationship between macrophages and CHI3L1. Furthermore, this article also provides a brief overview of the various mechanisms and inhibitors employed to inhibit CHI3L1 and disrupt its interaction with receptors. These endeavors highlight the pivotal roles of CHI3L1 and suggest therapeutic approaches targeting CHI3L1 in the development of metabolic diseases, neurodegenerative diseases, and cancers.
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Affiliation(s)
| | - Mingdong Huang
- College of Chemistry, Fuzhou University, Fuzhou 350116, China;
| | - Longguang Jiang
- College of Chemistry, Fuzhou University, Fuzhou 350116, China;
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Gündüz G, Beler M, Ünal İ, Cansız D, Emekli-Alturfan E, Kose KN. Endotoxin of Porphyromonas gingivalis amplifies the inflammatory response in hyperglycemia-induced zebrafish through a mechanism involving chitinase-like protein YKL-40 analogs. Toxicol Res 2023; 39:625-636. [PMID: 37779592 PMCID: PMC10541394 DOI: 10.1007/s43188-023-00190-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 05/04/2023] [Accepted: 05/10/2023] [Indexed: 10/03/2023] Open
Abstract
Porphyromonas gingivalis (P. gingivalis), a key pathogen in periodontal diseases, is also associated with hyperglycemia-associated systemic diseases, including diabetes mellitus (DM). Gingipains are the most important endotoxins of P. gingivalis, and in vivo studies using gingipains are scarce. Zebrafish (Danio rerio) is a vertebrate with high physiological and genetic homology with humans that has multiple co-orthologs for human genes, including inflammation-related proteins. The aim of our study was to determine the effects of gingipain in a hyperglycemia-induced zebrafish model by evaluating inflammation, oxidant-antioxidant status, and the cholinergic system. Adult zebrafish were grouped into the control group (C), hyperglycemia-induced group subjected to 15 days of overfeeding (OF), gingipain-injected group (GP), and gingipain-injected hyperglycemic group (OF + GP). At the end of 15 days, an oral glucose tolerance test (OGTT) was performed, and fasting blood glucose (FBG) levels were measured. Lipid peroxidation (LPO), nitric oxide (NO), glutathione (GSH), glutathione S-transferase, catalase, acetylcholinesterase (AChE), alkaline phosphatase (ALP), and sialic acid (SA) levels were determined spectrophotometrically in the hepatopancreas. The expression levels of tnf-⍺, il-1β, ins, crp, and the acute phase protein YKL-40 analogs chia.5 and chia.6 were evaluated by RT‒PCR. After two weeks of overfeeding, significantly increased weight gain, FBG, and OGTT confirmed that the zebrafish were hyperglycemic. Increased oxidative stress, inflammation, and AChE and ALP activities were observed in both the overfeeding and GP groups. Amplification of inflammation and oxidative stress was evident in the OF + GP group through increased expression of crp, il-1β, chia.5, and chia.6 and increased LPO and NO levels. Our results support the role of gingipains in the increased inflammatory response in hyperglycemia-associated diseases.
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Affiliation(s)
- Gizem Gündüz
- Department of Periodontology, Institute of Health Sciences, Marmara University, Istanbul, Turkey
| | - Merih Beler
- Department of Biochemistry, Institute of Health Sciences, Marmara University, Istanbul, Turkey
| | - İsmail Ünal
- Department of Biochemistry, Institute of Health Sciences, Marmara University, Istanbul, Turkey
| | - Derya Cansız
- Department of Biochemistry, Faculty of Medicine, Istanbul Medipol University, Istanbul, Turkey
| | - Ebru Emekli-Alturfan
- Department of Biochemistry, Faculty of Dentistry, Marmara University, Istanbul, Turkey
| | - Kemal Naci Kose
- Department of Periodontology, Faculty of Dentistry, Marmara University, Marmara University Basibuyuk Medical Campus, Basibuyuk, Maltepe, 34854 Istanbul, Turkey
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Bombaci A, Manera U, De Marco G, Casale F, Salamone P, Fuda G, Marchese G, Iazzolino B, Peotta L, Moglia C, Calvo A, Chiò A. Plasma CHI3L1 in Amyotrophic Lateral Sclerosis: A Potential Differential Diagnostic Biomarker. J Clin Med 2023; 12:jcm12062367. [PMID: 36983366 PMCID: PMC10058007 DOI: 10.3390/jcm12062367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 03/06/2023] [Accepted: 03/13/2023] [Indexed: 03/30/2023] Open
Abstract
(1) Background: Motor neuron diseases (MNDs) are fatal neurodegenerative diseases. Biomarkers could help with defining patients' prognoses and stratifications. Besides neurofilaments, chitinases are a promising family of possible biomarkers which correlate with neuroinflammatory status. We evaluated the plasmatic levels of CHI3L1 in MNDs, MND mimics, and healthy controls (HCs). (2) Methods: We used a sandwich ELISA to quantify the CHI3L1 in plasma samples from 44 MND patients, 7 hereditary spastic paraplegia (HSP) patients, 9 MND mimics, and 19 HCs. We also collected a ALSFRSr scale, MRC scale, spirometry, mutational status, progression rate (PR), blood sampling, and neuropsychological evaluation. (3) Results: The plasma levels of the CHI3L1 were different among groups (p = 0.005). Particularly, the MND mimics showed higher CHI3L1 levels compared with the MND patients and HCs. The CHI3L1 levels did not differ among PMA, PLS, and ALS, and we did not find a correlation among the CHI3L1 levels and clinical scores, spirometry parameters, PR, and neuropsychological features. Of note, the red blood cell count and haemoglobin was correlated with the CHI3L1 levels (respectively, p < 0.001, r = 0.63; p = 0.022, and r = 0.52). (4) Conclusions: The CHI3L1 plasma levels were increased in the MND mimics cohort compared with MNDs group. The increase of CHI3L1 in neuroinflammatory processes could explain our findings. We confirmed that the CHI3L1 plasma levels did not allow for differentiation between ALS and HCs, nor were they correlated with neuropsychological impairment.
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Affiliation(s)
- Alessandro Bombaci
- "Rita Levi Montalcini" Department of Neuroscience, University of Turin, 10126 Turin, Italy
| | - Umberto Manera
- "Rita Levi Montalcini" Department of Neuroscience, University of Turin, 10126 Turin, Italy
| | - Giovanni De Marco
- "Rita Levi Montalcini" Department of Neuroscience, University of Turin, 10126 Turin, Italy
| | - Federico Casale
- "Rita Levi Montalcini" Department of Neuroscience, University of Turin, 10126 Turin, Italy
| | - Paolina Salamone
- "Rita Levi Montalcini" Department of Neuroscience, University of Turin, 10126 Turin, Italy
| | - Giuseppe Fuda
- "Rita Levi Montalcini" Department of Neuroscience, University of Turin, 10126 Turin, Italy
| | - Giulia Marchese
- "Rita Levi Montalcini" Department of Neuroscience, University of Turin, 10126 Turin, Italy
| | - Barbara Iazzolino
- "Rita Levi Montalcini" Department of Neuroscience, University of Turin, 10126 Turin, Italy
| | - Laura Peotta
- "Rita Levi Montalcini" Department of Neuroscience, University of Turin, 10126 Turin, Italy
| | - Cristina Moglia
- "Rita Levi Montalcini" Department of Neuroscience, University of Turin, 10126 Turin, Italy
| | - Andrea Calvo
- "Rita Levi Montalcini" Department of Neuroscience, University of Turin, 10126 Turin, Italy
| | - Adriano Chiò
- "Rita Levi Montalcini" Department of Neuroscience, University of Turin, 10126 Turin, Italy
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11
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Zaoui M, Morel M, Louadj L, Ferrand N, Lamazière A, Uzan C, Canlorbe G, Atlan M, Sabbah M. Adipocytes secretome from normal and tumor breast favor breast cancer invasion by metabolic reprogramming. Clin Transl Oncol 2022; 25:1389-1401. [PMID: 36520383 DOI: 10.1007/s12094-022-03035-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 11/29/2022] [Indexed: 12/23/2022]
Abstract
BACKGROUND Adipose tissue is a major component of breast stroma. This study focused on delineating the effects of adipose stem cells (ASCs) derived from breast of healthy women and cancer patients with normal or tumor breast cells. METHODS The ASCs were induced to differentiate into adipocytes, and the subsequent adipocyte conditioned media (ACM) were evaluated for their fatty acid profile, adipokine secretion and influence on proliferation, migration and invasion on tumoral (MCF-7 and SUM159) and normal (HMEC) human breast cell lines. RESULTS An enrichment of arachidonic acid was observed in ACM from tumor tissues. Adipose tissues from tumor free secrete twice as much leptin than those from proximal or distal to the tumor. All ACMs display proliferative activity and favor invasiveness of SUM159 cells compared to MCF-7 and HMEC. All ACMs induced lipid droplets accumulation in MCF-7 cells and increased CD36 expression in tumor cells. CONCLUSION We conclude that among secreted factors analyzed, only arachidonic acid and leptin levels did discriminate ASCs from tumor-bearing and tumor-free breasts emphasizing the importance that other cell types could contribute to the adipose tissue secretome in a tumor context.
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Affiliation(s)
- Maurice Zaoui
- Team Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine (CRSA), Institut Universitaire de Cancérologie, Sorbonne University, INSERM UMR_S 938, 75012, Paris, France
| | - Mehdi Morel
- Team Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine (CRSA), Institut Universitaire de Cancérologie, Sorbonne University, INSERM UMR_S 938, 75012, Paris, France
| | - Lila Louadj
- Team Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine (CRSA), Institut Universitaire de Cancérologie, Sorbonne University, INSERM UMR_S 938, 75012, Paris, France
| | - Nathalie Ferrand
- Team Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine (CRSA), Institut Universitaire de Cancérologie, Sorbonne University, INSERM UMR_S 938, 75012, Paris, France
| | - Antonin Lamazière
- UMR 70203, Laboratory of Biomolecules, Institut National de La Santé Et de La Recherche Médicale (INSERM), École Normale Supérieure, AP-HP, 75012, Paris, France
| | - Catherine Uzan
- Team Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine (CRSA), Institut Universitaire de Cancérologie, Sorbonne University, INSERM UMR_S 938, 75012, Paris, France
- Department of Gynecological and Breast Surgery and Oncology, Assistance Publique des Hôpitaux de Paris (AP-HP)Pitié-Salpêtrière University Hospital, 75013, Paris, France
| | - Geoffroy Canlorbe
- Team Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine (CRSA), Institut Universitaire de Cancérologie, Sorbonne University, INSERM UMR_S 938, 75012, Paris, France
- Department of Gynecological and Breast Surgery and Oncology, Assistance Publique des Hôpitaux de Paris (AP-HP)Pitié-Salpêtrière University Hospital, 75013, Paris, France
| | - Michael Atlan
- Department of Plastic Surgery, Reconstructive, Aesthetic, Microsurgery and Tissue Regeneration, Tenon Hospital, Institut Universitaire de Cancérologie, AP-HP, 75020, Paris, France
| | - Michèle Sabbah
- Team Cancer Biology and Therapeutics, Centre de Recherche Saint-Antoine (CRSA), Institut Universitaire de Cancérologie, Sorbonne University, INSERM UMR_S 938, 75012, Paris, France.
- Centre National de la Recherche Scientifique (CNRS), 75012, Paris, France.
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12
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Krishnan A, Sharma H, Yuan D, Trollope AF, Chilton L. The Role of Epicardial Adipose Tissue in the Development of Atrial Fibrillation, Coronary Artery Disease and Chronic Heart Failure in the Context of Obesity and Type 2 Diabetes Mellitus: A Narrative Review. J Cardiovasc Dev Dis 2022; 9:jcdd9070217. [PMID: 35877579 PMCID: PMC9318726 DOI: 10.3390/jcdd9070217] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 06/28/2022] [Accepted: 06/28/2022] [Indexed: 12/07/2022] Open
Abstract
Cardiovascular diseases (CVDs) are a significant burden globally and are especially prevalent in obese and/or diabetic populations. Epicardial adipose tissue (EAT) surrounding the heart has been implicated in the development of CVDs as EAT can shift from a protective to a maladaptive phenotype in diseased states. In diabetic and obese patients, an elevated EAT mass both secretes pro-fibrotic/pro-inflammatory adipokines and forms intramyocardial fibrofatty infiltrates. This narrative review considers the proposed pathophysiological roles of EAT in CVDs. Diabetes is associated with a disordered energy utilization in the heart, which promotes intramyocardial fat and structural remodeling. Fibrofatty infiltrates are associated with abnormal cardiomyocyte calcium handling and repolarization, increasing the probability of afterdepolarizations. The inflammatory phenotype also promotes lateralization of connexin (Cx) proteins, undermining unidirectional conduction. These changes are associated with conduction heterogeneity, together creating a substrate for atrial fibrillation (AF). EAT is also strongly implicated in coronary artery disease (CAD); inflammatory adipokines from peri-vascular fat can modulate intra-luminal homeostasis through an “outside-to-inside” mechanism. EAT is also a significant source of sympathetic neurotransmitters, which promote progressive diastolic dysfunction with eventual cardiac failure. Further investigations on the behavior of EAT in diabetic/obese patients with CVD could help elucidate the pathogenesis and uncover potential therapeutic targets.
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Affiliation(s)
- Anirudh Krishnan
- College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia; (A.K.); (H.S.); (D.Y.)
| | - Harman Sharma
- College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia; (A.K.); (H.S.); (D.Y.)
| | - Daniel Yuan
- College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia; (A.K.); (H.S.); (D.Y.)
| | - Alexandra F. Trollope
- Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia;
| | - Lisa Chilton
- Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, College of Public Health, Medical and Veterinary Sciences, James Cook University, Townsville, QLD 4811, Australia
- Correspondence:
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13
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Porro C, La Torre ME, Tartaglia N, Benameur T, Santini M, Ambrosi A, Messina G, Cibelli G, Fiorelli A, Polito R, Messina G. The Potential Role of Nutrition in Lung Cancer Establishment and Progression. Life (Basel) 2022; 12:270. [PMID: 35207557 PMCID: PMC8877211 DOI: 10.3390/life12020270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 02/01/2022] [Accepted: 02/08/2022] [Indexed: 11/16/2022] Open
Abstract
Lung cancer is a devastating disease with a high incidence and low survival rates, so recent studies have focused on analyzing the risk factors that might prevent this disease from developing or have protective/therapeutic effects. Nutrition is an important key factor in the prevention and treatment of lung cancer. Various factors appear to be involved in the development of the latter, such as cigarette smoking or certain external environmental factors. The increase in oxidative stress is therefore an integral part of the carcinogenesis process. The biological role of bioactive factors derived from adipose tissue, mainly adipokines, is implicated in various cancers, and an increasing body of evidence has shown that certain adipocytokines contribute to the development, progression and prognosis of lung cancer. Not all adipokines stimulate tumor growth; in fact, adiponectin inhibits carcinogenesis by regulating both cell growth and the levels of inflammatory cytokines. Adiponectin expression is deregulated in several cancer types. Many nutritional factors have been shown to increase adiponectin levels and therefore could be used as a new therapeutic strategy for combating lung cancer. In addition, foods with antioxidant and anti-inflammatory properties play a key role in the prevention of many human diseases, including lung cancer. The purpose of this review is to analyze the role of diet in lung cancer in order to recommend dietary habit and lifestyle changes to prevent or treat this pathology.
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Affiliation(s)
- Chiara Porro
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy; (C.P.); (M.E.L.T.); (G.M.); (G.C.)
| | - Maria Ester La Torre
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy; (C.P.); (M.E.L.T.); (G.M.); (G.C.)
| | - Nicola Tartaglia
- Department of Medical Additionally, Surgical Sciences, University of Foggia, 71100 Foggia, Italy; (N.T.); (A.A.)
| | - Tarek Benameur
- Department of Biomedical Sciences, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia;
| | - Mario Santini
- Department of Translational Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.S.); (G.M.)
| | - Antonio Ambrosi
- Department of Medical Additionally, Surgical Sciences, University of Foggia, 71100 Foggia, Italy; (N.T.); (A.A.)
| | - Giovanni Messina
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy; (C.P.); (M.E.L.T.); (G.M.); (G.C.)
| | - Giuseppe Cibelli
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy; (C.P.); (M.E.L.T.); (G.M.); (G.C.)
| | - Alfonso Fiorelli
- Department of Translational Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.S.); (G.M.)
| | - Rita Polito
- Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy; (C.P.); (M.E.L.T.); (G.M.); (G.C.)
| | - Gaetana Messina
- Department of Translational Medicine, Università degli Studi della Campania “Luigi Vanvitelli”, 80138 Naples, Italy; (M.S.); (G.M.)
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14
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Sabaratnam R, Wojtaszewski JFP, Højlund K. Factors mediating exercise-induced organ crosstalk. Acta Physiol (Oxf) 2022; 234:e13766. [PMID: 34981891 DOI: 10.1111/apha.13766] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 10/11/2021] [Accepted: 01/01/2022] [Indexed: 12/21/2022]
Abstract
Exercise activates a plethora of metabolic and signalling pathways in skeletal muscle and other organs causing numerous systemic beneficial metabolic effects. Thus, regular exercise may ameliorate and prevent the development of several chronic metabolic diseases. Skeletal muscle is recognized as an important endocrine organ regulating systemic adaptations to exercise. Skeletal muscle may mediate crosstalk with other organs through the release of exercise-induced cytokines, peptides and proteins, termed myokines, into the circulation. Importantly, other tissues such as the liver and adipose tissue may also release cytokines and peptides in response to exercise. Hence, exercise-released molecules are collectively called exerkines. Moreover, extracellular vesicles (EVs), in the form of exosomes or microvesicles, may carry some of the signals involved in tissue crosstalk. This review focuses on the role of factors potentially mediating crosstalk between muscle and other tissues in response to exercise.
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Affiliation(s)
- Rugivan Sabaratnam
- Steno Diabetes Center Odense Odense University Hospital Odense C Denmark
- Section of Molecular Diabetes & Metabolism, Department of Clinical Research & Department of Molecular Medicine University of Southern Denmark Odense C Denmark
| | - Jørgen F. P. Wojtaszewski
- Section of Molecular Physiology Department of Nutrition, Exercise and Sports University of Copenhagen Copenhagen Denmark
| | - Kurt Højlund
- Steno Diabetes Center Odense Odense University Hospital Odense C Denmark
- Section of Molecular Diabetes & Metabolism, Department of Clinical Research & Department of Molecular Medicine University of Southern Denmark Odense C Denmark
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15
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Sianipar IR, Sestramita S, Pradnjaparamita T, Yunir E, Harbuwono DS, Soewondo P, Tahapary DL. The role of Intestinal-Fatty Acid Binding Proteins and Chitinase-3-Like Protein 1 across the spectrum of dysglycemia. Diabetes Metab Syndr 2022; 16:102366. [PMID: 34942410 DOI: 10.1016/j.dsx.2021.102366] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 12/07/2021] [Accepted: 12/09/2021] [Indexed: 11/15/2022]
Abstract
BACKGROUND AND AIMS Recent studies underlie the importance of intestinal permeability and chronic inflammation in the pathogenesis of T2DM. Our study compared the concentrations of FABP2 and YKL40 as markers of intestinal permeability and inflammation among normoglycemia, prediabetes and T2DM. METHODS We recruited 122 participants (45 normoglycemic, 26 prediabetes, and 51 T2DM) of whom we measured the fasting serum levels of FABP2 and YKL-40 using ELISA method. RESULTS The levels of FABP2 were significantly higher in the T2DM group [2.890 (1.880-4.070)] in comparison to both prediabetes [2.025 (1.145-2.343), p = 0.0085] and normoglycemia group [1.72 (1.250-2.645), p = 0.011]. The levels of YKL-40 were also significantly higher in the T2DM group [68.70 (44.61-166.6)] in comparison to both prediabetes [28.85 (20.64-41.53), p < 0.0001] and normoglycemia group [28.64 (19.25-43.87), p < 0.001]. CONCLUSIONS Our study observed that the levels of FABP2 and YKL-40 were highest in the T2DM group supporting the available evidences on the role of intestinal permeability disruption and chronic low-grade inflammation in the pathogenesis of T2DM.
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Affiliation(s)
- Imelda R Sianipar
- Department of Medical Physiology, Faculty of Medicine, Universitas Indonesia, Indonesia.
| | - Sestramita Sestramita
- Graduate Student of Master Program in Biomedical Science, Faculty of Medicine, Universitas Indonesia, Indonesia
| | - Tika Pradnjaparamita
- Metabolic, Cardiovascular and Aging Research Cluster, The Indonesian Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
| | - Em Yunir
- Metabolic, Cardiovascular and Aging Research Cluster, The Indonesian Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Division of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, dr. Cipto Mangunkusumo National General Hospital/Faculty of Medicine Universitas Indonesia, Indonesia
| | - Dante S Harbuwono
- Metabolic, Cardiovascular and Aging Research Cluster, The Indonesian Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Division of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, dr. Cipto Mangunkusumo National General Hospital/Faculty of Medicine Universitas Indonesia, Indonesia
| | - Pradana Soewondo
- Metabolic, Cardiovascular and Aging Research Cluster, The Indonesian Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Division of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, dr. Cipto Mangunkusumo National General Hospital/Faculty of Medicine Universitas Indonesia, Indonesia.
| | - Dicky L Tahapary
- Metabolic, Cardiovascular and Aging Research Cluster, The Indonesian Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Division of Endocrinology, Metabolism and Diabetes, Department of Internal Medicine, dr. Cipto Mangunkusumo National General Hospital/Faculty of Medicine Universitas Indonesia, Indonesia.
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16
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Zhou CD, Seah RL, Papatheodorou SI. The role of biomarker ykl-40 in risk stratification and diagnosis of gestational diabetes mellitus: A systematic review and meta-analysis. ENDOCRINE AND METABOLIC SCIENCE 2021. [DOI: 10.1016/j.endmts.2021.100094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
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17
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Serum YKL-40 Levels Are Associated with the Atherogenic Index of Plasma in Children. Mediators Inflamm 2020; 2020:8713908. [PMID: 33061832 PMCID: PMC7533750 DOI: 10.1155/2020/8713908] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 09/01/2020] [Accepted: 09/13/2020] [Indexed: 11/18/2022] Open
Abstract
YKL-40, also known as chitinase-3-like protein 1, is an inflammatory glycoprotein that is secreted by various cell types under acute, chronic, and subclinical inflammation conditions. Elevated serum YKL-40 levels are reportedly independently related to diabetes mellitus, coronary artery disease, acute myocardial infarction, and cardiovascular mortality in adults. Therefore, we aimed to investigate the relationship between serum YKL-40 levels, lipid abnormalities, and the atherogenic index of plasma (AIP) in children. We enrolled 479 children aged 10–12 years (mean age: 11.52) in this general population-based, cross-sectional study. All subjects completed questionnaires and were subjected to multifrequency bioelectrical impedance analysis (BIA) to measure their height, weight, and body mass index (BMI). We collected serum samples from all participants to measure YKL-40, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels. Mean serum YKL-40 levels were significantly higher in the low-HDL-C (p = 0.017) and high-TG (p = 0.010) groups but were not related to TC and LDL-C levels. YKL-40 levels were also higher in the high AIP group (p = 0.007). After adjusting for age, gender, and BMI z-score, the associations between serum YKL-40 levels and TG levels (p = 0.003), the TG-to-HDL-C ratio (p = 0.019), and the AIP value (p = 0.012) remained significant. Based on these findings, we suggest that serum YKL-40 may be a useful initial screening tool or follow-up risk indicator for lipid abnormalities, atherosclerosis, and cardiovascular disease in children and adolescents with risk factors, regardless of obesity.
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18
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YKL-40 as a novel biomarker in cardio-metabolic disorders and inflammatory diseases. Clin Chim Acta 2020; 511:40-46. [PMID: 33002471 DOI: 10.1016/j.cca.2020.09.035] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 09/25/2020] [Accepted: 09/25/2020] [Indexed: 02/07/2023]
Abstract
Dyslipidaemia is associated with numerous health problems that include the combination of insulin resistance, hypertension and obesity, ie, metabolic syndrome. Although the use of statins to decrease serum low density lipoprotein cholesterol (LDL-C) has been an effective therapeutic in treating atherosclerosis, the persistence of high atherosclerotic risk, ie, residual risk, is notable and is not simply explained as a phenomenon of dyslipidaemia. As such, it is imperative that we identify new biomarkers to monitor treatment and more accurately predict future cardiovascular events. This athero-protective strategy includes the assessment of novel inflammatory biomarkers such as YKL-40. Recent evidence has implicated YKL-40 in patients with inflammatory diseases and cardio-metabolic disorders, making it potentially useful to evaluate disease severity, prognosis and survival. In this review, we summarize role of YKL-40 in the pathogenesis of cardio-metabolic disorders and explore its use as a novel biomarker for monitoring athero-protective therapy.
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19
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Zhao T, Su Z, Li Y, Zhang X, You Q. Chitinase-3 like-protein-1 function and its role in diseases. Signal Transduct Target Ther 2020; 5:201. [PMID: 32929074 PMCID: PMC7490424 DOI: 10.1038/s41392-020-00303-7] [Citation(s) in RCA: 301] [Impact Index Per Article: 60.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 07/28/2020] [Accepted: 08/20/2020] [Indexed: 12/12/2022] Open
Abstract
Non-enzymatic chitinase-3 like-protein-1 (CHI3L1) belongs to glycoside hydrolase family 18. It binds to chitin, heparin, and hyaluronic acid, and is regulated by extracellular matrix changes, cytokines, growth factors, drugs, and stress. CHI3L1 is synthesized and secreted by a multitude of cells including macrophages, neutrophils, synoviocytes, chondrocytes, fibroblast-like cells, smooth muscle cells, and tumor cells. It plays a major role in tissue injury, inflammation, tissue repair, and remodeling responses. CHI3L1 has been strongly associated with diseases including asthma, arthritis, sepsis, diabetes, liver fibrosis, and coronary artery disease. Moreover, following its initial identification in the culture supernatant of the MG63 osteosarcoma cell line, CHI3L1 has been shown to be overexpressed in a wealth of both human cancers and animal tumor models. To date, interleukin-13 receptor subunit alpha-2, transmembrane protein 219, galectin-3, chemo-attractant receptor-homologous 2, and CD44 have been identified as CHI3L1 receptors. CHI3L1 signaling plays a critical role in cancer cell growth, proliferation, invasion, metastasis, angiogenesis, activation of tumor-associated macrophages, and Th2 polarization of CD4+ T cells. Interestingly, CHI3L1-based targeted therapy has been increasingly applied to the treatment of tumors including glioma and colon cancer as well as rheumatoid arthritis. This review summarizes the potential roles and mechanisms of CHI3L1 in oncogenesis and disease pathogenesis, then posits investigational strategies for targeted therapies.
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Affiliation(s)
- Ting Zhao
- Affiliated Cancer Hospital & Institute, Guangzhou Medical University, Guangzhou, China
| | - Zhongping Su
- Department of Biotherapy, Department of Geriatrics, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yingchang Li
- Affiliated Cancer Hospital & Institute, Guangzhou Medical University, Guangzhou, China
- Key Laboratory of Cell Homeostasis and Cancer Research of Guangdong Higher Education Institutes, Guangzhou Medical University, Guangzhou, China
| | - Xiaoren Zhang
- Affiliated Cancer Hospital & Institute, Guangzhou Medical University, Guangzhou, China
- Key Laboratory of Cell Homeostasis and Cancer Research of Guangdong Higher Education Institutes, Guangzhou Medical University, Guangzhou, China
| | - Qiang You
- Affiliated Cancer Hospital & Institute, Guangzhou Medical University, Guangzhou, China.
- Department of Biotherapy, Department of Geriatrics, Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
- Key Laboratory of Cell Homeostasis and Cancer Research of Guangdong Higher Education Institutes, Guangzhou Medical University, Guangzhou, China.
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20
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Wang S, Hu M, Qian Y, Jiang Z, Shen L, Fu L, Hu Y. CHI3L1 in the pathophysiology and diagnosis of liver diseases. Biomed Pharmacother 2020; 131:110680. [PMID: 32861071 DOI: 10.1016/j.biopha.2020.110680] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2020] [Revised: 08/17/2020] [Accepted: 08/20/2020] [Indexed: 02/07/2023] Open
Abstract
Chitinase 3-like protein 1(CHI3L1) participates in physiological and pathophysiological process, such as cell survival, cell proliferation, tissue remodeling, angiogenesis, etc. Some studies demonstrated that CHI3L1 is liver-enriched and has better application value in staging liver fibrosis than platelet ratio index(APRI) and fibrosis-4 index(FIB-4) and that CHI3L1 can be used in monitoring the prognosis of hepatocellular carcinoma (HCC). In this review, we summarized the pathophysiological role and the diagnostic value of CHI3L1 in liver fibrosis in different background and HCC.
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Affiliation(s)
- Shuwei Wang
- Department of Hepatology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, China; Medical School of Ningbo University, Ningbo 315211, China
| | - Mengyuan Hu
- Medical School of Ningbo University, Ningbo 315211, China
| | - Yunsong Qian
- Department of Hepatology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, China; Medical School of Ningbo University, Ningbo 315211, China
| | - Zhenluo Jiang
- Department of Hepatology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, China; Medical School of Ningbo University, Ningbo 315211, China
| | - Lili Shen
- Department of Hepatology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, China; Medical School of Ningbo University, Ningbo 315211, China
| | - Liyun Fu
- Department of Hepatology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, China; Ningbo Institute of Life and Health Industry, University of Chinese Academy of Science, Ningbo 315010, China; Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo 315010, China; Ningbo Clinical Research Center for Digestive System Tumors (Grant No.2019A21003), Ningbo 315010, China.
| | - Yaoren Hu
- Department of Hepatology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, China; Ningbo Institute of Life and Health Industry, University of Chinese Academy of Science, Ningbo 315010, China; Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo 315010, China; Ningbo Clinical Research Center for Digestive System Tumors (Grant No.2019A21003), Ningbo 315010, China.
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Lian C, Lou H, Zhang J, Tian H, Ou Q, Xu JY, Jin C, Gao F, Zhang J, Wang J, Li W, Xu G, Lu L, Xu GT. MicroRNA-24 protects retina from degeneration in rats by down-regulating chitinase-3-like protein 1. Exp Eye Res 2019; 188:107791. [PMID: 31491426 DOI: 10.1016/j.exer.2019.107791] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Revised: 08/12/2019] [Accepted: 09/02/2019] [Indexed: 12/27/2022]
Abstract
MicroRNAs (miRNAs) have been shown to play critical roles in the pathogenesis and progression of degenerative retinal diseases like age-related macular degeneration (AMD). In this study, we first demonstrated that miR-24 plays an important role in maintaining retinal structure and visual function of rats by targeting chitinase-3-like protein 1 (CHI3L1). In the retinal pigment epithelial (RPE) cells of Royal College of Surgeons (RCS) rats, an animal model of genetic retinal degeneration (RD), miR-24 was found lower and CHI3L1 level was higher in comparison with those in Sprague-Dawley (SD) rats. Other changes in the eyes of RCS rats include activated AKT/mTOR and ERK pathways and abnormal autophagy in the RPE cells. Such roles of miR-24 and CHI3L1 were further confirmed in RCS rats by subretinal injection of agomiR-24, which decreased CHI3L1 level and preserved retinal structure and function. Upstream, NF-κB was identified as the regulator of miR-24 in the RPE cells of these rats. On the other hand, in SD rats, intraocular treatment of antagomiR-24 induced pathological changes similar to those in RCS rats. The results revealed the protective roles for miR-24 to RPE cells and a mechanism for RD in RCS rats was proposed: extracellular stress stimuli first activate the NF-κB signaling pathway, which lowers miR-24 expression so that CHI3L1 increased. CHI3L1 sequentially results in aberrant autophagy and RPE dysfunction by activating AKT/mTOR and ERK pathways. Taken together, although the possibility, that the therapeutic effects in RCS rats are caused by other transcriptional changes regulated by miR-24, cannot be excluded, these findings indicate that miR-24 protects rat retina by targeting CHI3L1. Thus, miR-24 and CHI3L1 might be the targets for developing more effective therapy for degenerative retinal diseases like AMD.
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Affiliation(s)
- Chunpin Lian
- Department of Ophthalmology of Shanghai Tenth People's Hospital, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, 200092, China; Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, China
| | - Hui Lou
- Department of Ophthalmology, the Second Affiliated Hospital of Soochow University, Suzhou, 215004, China
| | - Jingfa Zhang
- Department of Ophthalmology of Shanghai Tenth People's Hospital, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, 200092, China; Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Haibin Tian
- Department of Ophthalmology of Shanghai Tenth People's Hospital, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, 200092, China; Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, China
| | - Qingjian Ou
- Department of Ophthalmology of Shanghai Tenth People's Hospital, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, 200092, China; Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, China
| | - Jing-Ying Xu
- Department of Ophthalmology of Shanghai Tenth People's Hospital, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, 200092, China; Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, China
| | - Caixia Jin
- Department of Ophthalmology of Shanghai Tenth People's Hospital, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, 200092, China; Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, China
| | - Furong Gao
- Department of Ophthalmology of Shanghai Tenth People's Hospital, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, 200092, China; Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, China
| | - Jieping Zhang
- Department of Ophthalmology of Shanghai Tenth People's Hospital, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, 200092, China; Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, China
| | - Juan Wang
- Department of Ophthalmology of Shanghai Tenth People's Hospital, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, 200092, China; Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, China
| | - Weiye Li
- Department of Ophthalmology of Shanghai Tenth People's Hospital, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, 200092, China; Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, China; Department of Ophthalmology, Drexel University College of Medicine, Philadelphia, PA, 19129, USA
| | - Guoxu Xu
- Department of Ophthalmology, the Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
| | - Lixia Lu
- Department of Ophthalmology of Shanghai Tenth People's Hospital, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, 200092, China; Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, China.
| | - Guo-Tong Xu
- Department of Ophthalmology of Shanghai Tenth People's Hospital, Tongji Eye Institute, Tongji University School of Medicine, Shanghai, 200092, China; Laboratory of Clinical Visual Science, Department of Regenerative Medicine, and Stem Cell Research Center, and Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, China; Collaborative Innovation Center for Brain Science, Tongji University, Shanghai, 200092, China.
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Yeo IJ, Lee CK, Han SB, Yun J, Hong JT. Roles of chitinase 3-like 1 in the development of cancer, neurodegenerative diseases, and inflammatory diseases. Pharmacol Ther 2019; 203:107394. [PMID: 31356910 DOI: 10.1016/j.pharmthera.2019.107394] [Citation(s) in RCA: 97] [Impact Index Per Article: 16.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/12/2019] [Indexed: 02/07/2023]
Abstract
Chitinase 3-like 1 (CHI3L1) is a secreted glycoprotein that mediates inflammation, macrophage polarization, apoptosis, and carcinogenesis. The expression of CHI3L1 is strongly increased by various inflammatory and immunological conditions, including rheumatoid arthritis, multiple sclerosis, Alzheimer's disease, and several cancers. However, its physiological and pathophysiological roles in the development of cancer and neurodegenerative and inflammatory diseases remain unclear. Several studies have reported that CHI3L1 promotes cancer proliferation, inflammatory cytokine production, and microglial activation, and that multiple receptors, such as advanced glycation end product, syndecan-1/αVβ3, and IL-13Rα2, are involved. In addition, the pro-inflammatory action of CHI3L1 may be mediated via the protein kinase B and phosphoinositide-3 signaling pathways and responses to various pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-6, and interferon-γ. Therefore, CHI3L1 could contribute to a vast array of inflammatory diseases. In this article, we review recent findings regarding the roles of CHI3L1 and suggest therapeutic approaches targeting CHI3L1 in the development of cancers, neurodegenerative diseases, and inflammatory diseases.
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Affiliation(s)
- In Jun Yeo
- College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31, Osongsaengmyeong 1-ro, Osong-eup, Cheongju-si, Chungbuk 28160, Republic of Korea
| | - Chong-Kil Lee
- College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31, Osongsaengmyeong 1-ro, Osong-eup, Cheongju-si, Chungbuk 28160, Republic of Korea
| | - Sang-Bae Han
- College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31, Osongsaengmyeong 1-ro, Osong-eup, Cheongju-si, Chungbuk 28160, Republic of Korea
| | - Jaesuk Yun
- College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31, Osongsaengmyeong 1-ro, Osong-eup, Cheongju-si, Chungbuk 28160, Republic of Korea.
| | - Jin Tae Hong
- College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31, Osongsaengmyeong 1-ro, Osong-eup, Cheongju-si, Chungbuk 28160, Republic of Korea.
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Li L, Pan Z, Yang X. Key genes and co-expression network analysis in the livers of type 2 diabetes patients. J Diabetes Investig 2019; 10:951-962. [PMID: 30592156 PMCID: PMC6626963 DOI: 10.1111/jdi.12998] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 12/03/2018] [Accepted: 12/25/2018] [Indexed: 12/17/2022] Open
Abstract
AIMS/INTRODUCTION The incidence of type 2 diabetes is increasing worldwide. Hepatic insulin resistance and liver lipid accumulation contributes to type 2 diabetes development. The aim of the present study was to investigate the key gene pathways and co-expression networks in the livers of type 2 diabetes patients. MATERIALS AND METHODS Dataset GSE15653 containing nine healthy individuals and nine type 2 diabetes patients was downloaded from the National Center for Biotechnology Information Gene Expression Omnibus database. Differentially expressed genes were obtained from the livers of type 2 diabetes patients, annotated pathway enrichment and protein-protein interaction network analysis. Next, functional modules and transcription factor networks were constructed. Gene co-expression networks were analyzed by weighted correlation network analysis to identify key modules related to clinical traits, and the candidate key genes were validated in hepatic insulin resistance models in vitro. RESULTS A total of 778 differentially expressed genes were filtered in the livers of type 2 diabetes patients, pathway enrichment analysis identified ke y pathways, such as the mitogen-activated protein kinase signaling pathway, Hippo signaling pathway and hypoxia-inducible factor-1 signaling pathway, that were associated with type 2 diabetes. Several transcription factors of three functional modules identified from protein-protein interaction networks are likely to be implicated in type 2 diabetes. Furthermore, weighted correlation network analysis identified five modules that were shown to be highly correlated with type 2 diabetes and other clinical traits. Functional annotation showed that these modules were mainly enriched in pathways such as metabolic pathways, phosphoinositide 3-kinase-protein kinase B signaling pathway and natural killer cell-mediated cytotoxicity. UBE2M and GPER were upregulated in L02 and HepG2 models, whereas P2RY11 only upregulated in L02 model, and UBE2N only downregulated in HepG2 model at a significant level. CONCLUSIONS These results would offer new insights into hepatic insulin resistance, type 2 diabetes pathogenesis, development and drug discovery.
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Affiliation(s)
- Lu Li
- Department of PharmacyThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouChina
| | - Zongfu Pan
- Department of PharmacyZhejiang Cancer HospitalHangzhouChina
| | - Xi Yang
- Department of PharmacyThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouChina
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Kulkarni NB, Ganu MU, Godbole SG, Deo SS. Assessment of potential biomarkers of atherosclerosis in Indian patients with type 2 diabetes mellitus. Indian J Med Res 2018; 147:169-176. [PMID: 29806605 PMCID: PMC5991114 DOI: 10.4103/ijmr.ijmr_852_16] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
Background & objectives: Various biological markers of subclinical atherosclerosis have been proposed to predict cardiovascular events in patients with diabetes mellitus (DM). However, there are only a few clinical studies assessing the role of invasive biomarkers [CD-36, peroxisome proliferator-activated receptor gamma (PPAR-γ) and YKL-40] in Indian patients with type 2 DM (T2DM). Hence, the present study was conducted to assess protein levels and gene expression of CD-36, PPAR-γ and YKL-40 in patients with T2DM and compare that with hypertensive and healthy controls. Methods: All the participants were subjected to medical history, anthropometric measurements and biochemical and biomarker (ELISA and real-time polymerase chain reaction) estimations. The study groups consisted of patients with T2DM (>5 yr) with hypertension (n=55), patients with T2DM (<2 yr) without hypertension (n=28), hypertensive controls (n=31) and healthy controls (n=30). Results: Gene expressions of YKL-40 and CD36 were significantly higher in patients with T2DM (>5 yr) with hypertension compared to healthy controls (P=0.006). In addition, a significant increase in serum levels of sCD36, PPAR-γ and YKL-40 was observed in patients with T2DM (>5 yr) with hypertension compared to healthy controls (P< 0.05). Serum levels as well as gene expression of CD36 showed significant correlation with serum levels as well as gene expression of PPAR-γ (ρ=0.45 and ρ=0.51; P< 0.001), respectively. Interpretation & conclusions: CD36 and YKL-40 may be potential inflammatory biomarkers for early onset of atherosclerosis in patients with T2DM.
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Affiliation(s)
- Namrata Bindurao Kulkarni
- Sir HN Medical Research Society, Sir HN Reliance Foundation Hospital & Research Centre, Mumbai, India
| | - Meghana Ulhas Ganu
- Sir HN Medical Research Society, Sir HN Reliance Foundation Hospital & Research Centre, Mumbai, India
| | - Sanjay Ganpati Godbole
- Sir HN Medical Research Society, Sir HN Reliance Foundation Hospital & Research Centre, Mumbai, India
| | - Sudha S Deo
- Sir HN Medical Research Society, Sir HN Reliance Foundation Hospital & Research Centre, Mumbai, India
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Unamuno X, Gómez-Ambrosi J, Rodríguez A, Becerril S, Frühbeck G, Catalán V. Adipokine dysregulation and adipose tissue inflammation in human obesity. Eur J Clin Invest 2018; 48:e12997. [PMID: 29995306 DOI: 10.1111/eci.12997] [Citation(s) in RCA: 411] [Impact Index Per Article: 58.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Accepted: 07/10/2018] [Indexed: 12/13/2022]
Abstract
Obesity, a worldwide epidemic, confers increased risk for multiple serious conditions, including type 2 diabetes, cardiovascular diseases, nonalcoholic fatty liver disease and cancer. Adipose tissue is considered one of the largest endocrine organs in the body as well as an active tissue for cellular reactions and metabolic homeostasis rather than an inert tissue for energy storage. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a large number of hormones, cytokines, extracellular matrix proteins and growth and vasoactive factors, collectively termed adipokines that influence a variety of physiological and pathophysiological processes. In the obese state, excessive visceral fat accumulation causes adipose tissue dysfunctionality that strongly contributes to the onset of obesity-related comorbidities. The mechanisms underlying adipose tissue dysfunction include adipocyte hypertrophy and hyperplasia, increased inflammation, impaired extracellular matrix remodelling and fibrosis together with an altered secretion of adipokines. This review describes how adipose tissue becomes inflamed in obesity and summarizes key players and molecular mechanisms involved in adipose inflammation.
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Affiliation(s)
- Xabier Unamuno
- Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.,CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain
| | - Javier Gómez-Ambrosi
- Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.,CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.,Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - Amaia Rodríguez
- Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.,CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.,Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - Sara Becerril
- Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.,CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.,Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - Gema Frühbeck
- Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.,CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.,Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain.,Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, Pamplona, Spain
| | - Victoria Catalán
- Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain.,CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.,Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
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YKL-40: A biomarker for early nephropathy in type 2 diabetic patients and its association with inflammatory cytokines. Immunobiology 2018; 223:718-727. [PMID: 30077474 DOI: 10.1016/j.imbio.2018.07.020] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Revised: 07/17/2018] [Accepted: 07/18/2018] [Indexed: 12/14/2022]
Abstract
Diabetic Nephropathy (DN) is an important cause of morbidity and death amongst diabetes. Persistent micro and macroalbuminuria are well known predictors of DN leading to progressive end-stage renal disease. However, albuminuria has several limitations. Increasing evidences show that YKL-40 is highly expressed in variety of inflammatory diseases and also recognized as a non-invasive prognostic biomarker for inflammation. In the present study, we measured plasma YKL-40 levels in different stages of albuminuria and assessed its diagnostic accuracy as a biomarker for DN and correlated with different families of circulatory cytokines. A total of 306 subjects were recruited and divided into three groups [Group-I, control (n = 83), Group-II, Normoalbuminuria (n = 81), Group-III, DN (n = 142)]. Group-III is further subdivided into: Group-IIIa, microalbuminuria (n = 73), Group-IIIb, macroalbuminuria (n = 69). The median levels of YKL-40 (p = 0.001) showed a marked stepwise increase from normo to macroalbuminuria and positively correlated with eGFR. The AUCROC for YKL-40 was found to be high [0.95; (95% CI: 0.88-1.0)], when compared to other acute phase markers. Plasma YKL-40 showed a positive correlation with LIGHT/TNFSF14, sIL-6Ra, gp130/sIL-6Rβ, IFN-β, IL-8, TNFSF14, sCD-30 and eGFR meanwhile a negative correlation with TWEAK/TNFSF12, IL-7 like cytokine and IFN-λ2. Plasma YKL-40 could be a potential biomarker for early diagnosis of incipient DN among South Indian population.
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Sabaratnam R, Pedersen AJT, Kristensen JM, Handberg A, Wojtaszewski JFP, Højlund K. Intact regulation of muscle expression and circulating levels of myokines in response to exercise in patients with type 2 diabetes. Physiol Rep 2018; 6:e13723. [PMID: 29924476 PMCID: PMC6009776 DOI: 10.14814/phy2.13723] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2018] [Revised: 05/06/2018] [Accepted: 05/08/2018] [Indexed: 12/17/2022] Open
Abstract
Regular exercise plays an important role in the prevention and treatment of type 2 diabetes (T2D). The synthesis and secretion of myokines in response to contraction may contribute to the beneficial metabolic effects of exercise. However, some exercise-induced responses may be attenuated in T2D. Here, we investigated whether the effect of acute exercise on selected myokines are impaired in T2D. Skeletal muscle biopsies and blood samples were obtained from 13 men with T2D and 14 weight-matched, glucose-tolerant men before, immediately after and 3-h after acute exercise (60 min cycling) to examine muscle expression and plasma/serum levels of selected myokines. One-hour of exercise increased muscle expression of IL6, FGF21, ANGPTL4, CHI3L1, CTGF and CYR61, of which FGF21, ANGPTL4 and CHI3L1 increased further 3-h into recovery, whereas expression of IL6, CYR61, and CTGF returned to baseline levels. There was no immediate effect of exercise on IL15 expression, but it decreased 3-h into recovery. Plasma IL-6 increased robustly, whereas circulating levels of FGF21, ANGPTL4, IL-15, and CHI3L1 increased only modestly in response to exercise. All returned toward baseline levels 3-h into recovery except for plasma ANGPTL4, which increased further. No significant differences in these responses to exercise were observed between the groups. Our results demonstrate that muscle expression and circulating levels of selected known and putative myokines were equally regulated by acute exercise in patients with T2D and weight-matched controls. This suggests that the potential beneficial metabolic effects of these myokines are not impaired in patients with T2D.
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Affiliation(s)
- Rugivan Sabaratnam
- Section of Molecular Diabetes & MetabolismInstitute of Clinical ResearchInstitute of Molecular MedicineUniversity of Southern DenmarkOdense CDenmark
- Department of EndocrinologyOdense University HospitalOdense CDenmark
| | | | - Jonas M. Kristensen
- Section of Molecular PhysiologyDepartment of Nutrition, Exercise and SportsUniversity of CopenhagenCopenhagenDenmark
| | - Aase Handberg
- Department of Clinical BiochemistryAalborg University HospitalAalborgDenmark
- Department of Clinical MedicineAalborg UniversityAalborgDenmark
| | - Jørgen F. P. Wojtaszewski
- Section of Molecular PhysiologyDepartment of Nutrition, Exercise and SportsUniversity of CopenhagenCopenhagenDenmark
| | - Kurt Højlund
- Section of Molecular Diabetes & MetabolismInstitute of Clinical ResearchInstitute of Molecular MedicineUniversity of Southern DenmarkOdense CDenmark
- Department of EndocrinologyOdense University HospitalOdense CDenmark
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Coriati A, Massé C, Ménard A, Bouvet GF, Berthiaume Y. Neutrophils as a Potential Source of Chitinase-3-like Protein 1 in Cystic Fibrosis. Inflammation 2018; 41:1631-1639. [DOI: 10.1007/s10753-018-0806-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Höbaus C, Tscharre M, Herz CT, Pesau G, Wrba T, Koppensteiner R, Schernthaner GH. YKL-40 levels increase with declining ankle-brachial index and are associated with long-term cardiovascular mortality in peripheral arterial disease patients. Atherosclerosis 2018; 274:152-156. [PMID: 29783062 DOI: 10.1016/j.atherosclerosis.2018.05.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Revised: 04/26/2018] [Accepted: 05/02/2018] [Indexed: 01/15/2023]
Abstract
BACKGROUND AND AIMS YKL-40 is an inflammatory marker secreted by macrophages and is expressed in atherosclerotic plaques. YKL-40 increases in coronary artery disease (CAD) with poor coronary collateral vessel development. Higher levels are linked to reduced survival in CAD patients. Studies evaluating YKL-40 in patients with peripheral arterial disease (PAD) are scarce. This study aims to elucidate a possible link between YKL-40 and PAD severity as well as cardiovascular long-term mortality. METHODS YKL-40 was measured at baseline in 365 elderly PAD patients (age 69 ± 10.4, 33.7% women, Fontaine stage I-II) by bead-based multiplex assay. Patients were followed for seven years to assess long-term cardiovascular and all-cause survival by Kaplan-Meier and Cox regression. RESULTS YKL-40 levels were associated with declining ankle-brachial index (ABI) in PAD patients without Moenckeberg's mediasclerosis (R = -0.189, p=0.002). PAD patients with mediasclerosis exhibited higher YKL-40 levels (p=0.002). Baseline YKL-40 levels were significantly associated with cardiovascular mortality (HR 1.52 (1.21-1.91), p < 0.001) and all-cause mortality (HR 1.45 (1.20-1.75), p < 0.001) over a seven-year observation period. After multivariable adjustment for gender, patient age, known carotid artery disease, known coronary artery disease, smoking status, systolic blood pressure, HbA1c, low density lipoprotein cholesterol, estimated glomerular filtration rate, aspartate aminotransferase, and C-reactive protein, YKL-40 remained significantly associated with cardiovascular (HR 1.34 (1.02-1.75), p=0.033) and all-cause mortality (HR 1.25 (1.01-1.55), p=0.039). CONCLUSIONS Increased YKL-40 levels are independently associated with poor long-term cardiovascular survival in peripheral arterial disease patients. Furthermore, YKL-40 correlates with patients' ABI in PAD in the absence of mediasclerosis.
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Affiliation(s)
- Clemens Höbaus
- Division of Angiology, Medicine II, Medical University Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Maximilian Tscharre
- 3rd Medical Department with Cardiology and Intensive Care Medicine, Wilhelminenspital, Montleartstraße 37, 1160, Vienna, Austria
| | - Carsten Thilo Herz
- Division of Endocrinology and Metabolism, Medicine III, Medical University Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Gerfried Pesau
- Division of Angiology, Medicine II, Medical University Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Thomas Wrba
- IT4Science, IT-Systems & Communications, Medical University Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Renate Koppensteiner
- Division of Angiology, Medicine II, Medical University Vienna, Spitalgasse 23, 1090, Vienna, Austria
| | - Gerit-Holger Schernthaner
- Division of Angiology, Medicine II, Medical University Vienna, Spitalgasse 23, 1090, Vienna, Austria.
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Abe K, Nakamura Y, Yamauchi K, Maemondo M. Role of genetic variations of chitinase 3- like 1 in bronchial asthmatic patients. Clin Mol Allergy 2018; 16:9. [PMID: 29618952 PMCID: PMC5880007 DOI: 10.1186/s12948-018-0086-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Accepted: 03/20/2018] [Indexed: 02/07/2023] Open
Abstract
Background Single nucleotide polymorphisms (SNPs) in chitinase 3-like 1 (CHI3L1) are associated with bronchial severity and pulmonary function. CHI3L1 proteins are involved in both innate and adaptive immune responses; however, to date, the correlation of these SNPs and their age of onset of bronchial asthma has not been demonstrated. Methods To address the role of these genetic variations, 390 patients with well-controlled bronchial asthma and living in Japan were recruited, genotyped, and had a pulmonary function test performed on them in this study. To analyze the concentration levels of CHI3L1 protein, bronchial lavage fluids were examined. Results Forced expiratory volume in one second, %predicted (%FEV1), was significantly decreased in homozygotes of rs1214194 compared to heterozygotes and wild type. The age of onset of adult bronchial asthma was significantly younger in GG homozygotes of rs4950928 and AA homozygotes of rs1214194 than in the other two genotypes. The concentration of CHI3L1 protein in bronchial lavage fluid increased in both homozygotes of rs4950928 and rs1214194. Conclusions Our study demonstrated that the homozygotes of rs4950928 and rs1214194 of CHI3L1 might predict an early onset of bronchial asthma and have the propensity to promote airway remodeling. Trial registration JMA-IIA00045 remodeling-ICS
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Affiliation(s)
- Kazuyuki Abe
- 1Division of Pulmonary Medicine, Allergy, and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, 0208505 Japan
| | - Yutaka Nakamura
- 2Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, 1-1-5 Sendagi, Tokyo, 1138603 Japan
| | - Kohei Yamauchi
- 1Division of Pulmonary Medicine, Allergy, and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, 0208505 Japan
| | - Makoto Maemondo
- 1Division of Pulmonary Medicine, Allergy, and Rheumatology, Department of Internal Medicine, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, 0208505 Japan
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Association of vascular indices with novel circulating biomarkers as prognostic factors for cardiovascular complications in patients with type 2 diabetes mellitus. Clin Biochem 2018; 53:31-37. [DOI: 10.1016/j.clinbiochem.2017.12.010] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Revised: 12/15/2017] [Accepted: 12/26/2017] [Indexed: 11/22/2022]
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Cornelis MC, Gustafsson S, Ärnlöv J, Elmståhl S, Söderberg S, Sundström J, Michaëlsson K, Lind L, Ingelsson E. Targeted proteomic analysis of habitual coffee consumption. J Intern Med 2018; 283:200-211. [PMID: 29044854 DOI: 10.1111/joim.12703] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
BACKGROUND Coffee drinking has been implicated in mortality and a variety of diseases but potential mechanisms underlying these associations are unclear. Large-scale systems epidemiological approaches may offer novel insights to mechanisms underlying associations of coffee with health. OBJECTIVE We performed an analysis of known and novel protein markers linked to cardiovascular disease and their association with habitual coffee intake in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS, n = 816) and followed up top proteins in the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 635) and EpiHealth (n = 2418). METHODS In PIVUS and ULSAM, coffee intake was measured by 7-day dietary records whilst a computer-based food frequency questionnaire was used in EpiHealth. Levels of up to 80 proteins were assessed in plasma by a proximity extension assay. RESULTS Four protein-coffee associations adjusted for age, sex, smoking and BMI, met statistical significance in PIVUS (FDR < 5%, P < 2.31 × 10-3 ): leptin (LEP), chitinase-3-like protein 1 (CHI3L), tumour necrosis factor (TNF) receptor 6 and TNF-related apoptosis-inducing ligand. The inverse association between coffee intake and LEP replicated in ULSAM (β, -0.042 SD per cup of coffee, P = 0.028) and EpiHealth (β, -0.025 SD per time of coffee, P = 0.004). The negative coffee-CHI3L association replicated in EpiHealth (β, -0.07, P = 1.15 × 10-7 ), but not in ULSAM (β, -0.034, P = 0.16). CONCLUSIONS The current study supports an inverse association between coffee intake and plasma LEP and CHI3L1 levels. The coffee-CHI3L1 association is novel and warrants further investigation given links between CHI3L1 and health conditions that are also potentially influenced by coffee.
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Affiliation(s)
- M C Cornelis
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
| | - S Gustafsson
- Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | - J Ärnlöv
- Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.,School of Health and Social Sciences, Dalarna University, Falun, Sweden
| | - S Elmståhl
- Department of Clinical Sciences, Division of Geriatric Medicine, Lund University, Malmö University Hospital, Malmö, Sweden
| | - S Söderberg
- Department of Public Health and Clinical Medicine, Cardiology, Umeå University, Umeå, Sweden
| | - J Sundström
- Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.,Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
| | - K Michaëlsson
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - L Lind
- Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden
| | - E Ingelsson
- Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.,Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA
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Toloza FJK, Pérez-Matos MC, Ricardo-Silgado ML, Morales-Álvarez MC, Mantilla-Rivas JO, Pinzón-Cortés JA, Pérez-Mayorga M, Arévalo-García ML, Tolosa-González G, Mendivil CO. Comparison of plasma pigment epithelium-derived factor (PEDF), retinol binding protein 4 (RBP-4), chitinase-3-like protein 1 (YKL-40) and brain-derived neurotrophic factor (BDNF) for the identification of insulin resistance. J Diabetes Complications 2017. [PMID: 28648555 DOI: 10.1016/j.jdiacomp.2017.06.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
AIMS To evaluate and compare the association of four potential insulin resistance (IR) biomarkers (pigment-epithelium-derived factor [PEDF], retinol-binding-protein-4 [RBP-4], chitinase-3-like protein 1 [YKL-40] and brain-derived neurotrophic factor [BDNF]) with objective measures of IR. METHODS We studied 81 subjects with different metabolic profiles. All participants underwent a 5-point OGTT with calculation of multiple IR indexes. A subgroup of 21 participants additionally underwent a hyperinsulinemic-euglycemic clamp. IR was defined as belonging to the highest quartile of incremental area under the insulin curve (iAUCins), or to the lowest quartile of the insulin sensitivity index (ISI). RESULTS PEDF was associated with adiposity variables. PEDF and RBP4 increased linearly across quartiles of iAUCins (for PEDF p-trend=0.029; for RBP-4 p-trend=0.053). YKL-40 and BDNF were not associated with any adiposity or IR variable. PEDF and RBP-4 levels identified individuals with IR by the iAUCins definition: A PEDF cutoff of 11.9ng/mL had 60% sensitivity and 68% specificity, while a RBP-4 cutoff of 71.6ng/mL had 70% sensitivity and 57% specificity. In multiple regression analyses simultaneously including clinical variables and the studied biomarkers, only BMI, PEDF and RBP-4 remained significant predictors of IR. CONCLUSIONS Plasma PEDF and RBP4 identified IR in subjects with no prior diagnosis of diabetes.
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Affiliation(s)
- F J K Toloza
- Universidad de los Andes, School of Medicine, Bogotá, Colombia
| | - M C Pérez-Matos
- Universidad de los Andes, School of Medicine, Bogotá, Colombia
| | | | | | | | | | - M Pérez-Mayorga
- Universidad Militar Nueva Granada, School of Medicine, Bogotá, Colombia
| | - M L Arévalo-García
- Fundación Santa Fe de Bogotá, Section of Endocrinology, Bogotá, Colombia
| | - G Tolosa-González
- Fundación Santa Fe de Bogotá, Section of Endocrinology, Bogotá, Colombia
| | - C O Mendivil
- Universidad de los Andes, School of Medicine, Bogotá, Colombia; Fundación Santa Fe de Bogotá, Section of Endocrinology, Bogotá, Colombia.
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Vela D, Leshoski J, Vela Z, Jakupaj M, Mladenov M, Sopi RB. Insulin treatment corrects hepcidin but not YKL-40 levels in persons with type 2 diabetes mellitus matched by body mass index, waist-to-height ratio, C-reactive protein and Creatinine. BMC Endocr Disord 2017; 17:53. [PMID: 28841871 PMCID: PMC5574085 DOI: 10.1186/s12902-017-0204-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Accepted: 08/21/2017] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND It has been shown that hepcidin and YKL-40 levels change in persons with insulin resistance in different circumstances. However, variations of the levels of these parameters through the stages of prediabetes and type 2 diabetes mellitus are unclear. We hypothesized that hepcidin levels will decrease in persons with prediabetes, while these levels will tend to correct when persons with diabetes are treated with insulin. Finally we sought to determine the levels of YKL-40 in all groups of participants included in the study. METHODS Serum hepcidin levels and YKL-40 levels were measured in control group (n = 20), persons with prediabetes (n = 30) and persons with diabetes on insulin therapy (n = 30) using ELISA method. Patients in all three groups were matched by Body Mass Index, Waist-to-Height Ratio, C-Reactive Protein and creatinine levels. RESULTS Hepcidin levels were lower in persons with prediabetes compared to control, while persons with diabetes on insulin therapy had higher values than those with prediabetes (p = 0,00001). YKL-40 levels showed no significant changes. CONCLUSIONS Serum hepcidin levels in matched persons with prediabetes are a stronger marker of early changes in glucose metabolism compared to YKL-40 levels. Also, treatment with insulin corrects hepcidin levels, but not YKL-40 levels. Correcting levels of hepcidin is important for reducing iron-overload, which is a risk factor for diabetes.
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Affiliation(s)
- Driton Vela
- Faculty of Medicine, University of Prishtina, Martyr’s Boulevard n.n, 10000 Prishtina, Kosovo
| | - Jovica Leshoski
- Institute of Biology, Faculty of Natural Sciences, “Sts. Cyril and Methodius” University, Skopje, 1000 Macedonia
| | - Zana Vela
- Faculty of Medicine, University of Prishtina, Martyr’s Boulevard n.n, 10000 Prishtina, Kosovo
| | - Muharrem Jakupaj
- Faculty of Medicine, University of Prishtina, Martyr’s Boulevard n.n, 10000 Prishtina, Kosovo
| | - Mitko Mladenov
- Institute of Biology, Faculty of Natural Sciences, “Sts. Cyril and Methodius” University, Skopje, 1000 Macedonia
| | - Ramadan B. Sopi
- Faculty of Medicine, University of Prishtina, Martyr’s Boulevard n.n, 10000 Prishtina, Kosovo
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Labrecque J, Laforest S, Michaud A, Biertho L, Tchernof A. Impact of Bariatric Surgery on White Adipose Tissue Inflammation. Can J Diabetes 2017; 41:407-417. [PMID: 28365202 DOI: 10.1016/j.jcjd.2016.12.003] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Revised: 09/23/2016] [Accepted: 12/05/2016] [Indexed: 12/14/2022]
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Deng X, Liu Y, Luo M, Wu J, Ma R, Wan Q, Wu J. Circulating miRNA-24 and its target YKL-40 as potential biomarkers in patients with coronary heart disease and type 2 diabetes mellitus. Oncotarget 2017; 8:63038-63046. [PMID: 28968969 PMCID: PMC5609901 DOI: 10.18632/oncotarget.18593] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2017] [Accepted: 05/23/2017] [Indexed: 12/11/2022] Open
Abstract
Type 2 diabetes mellitus (DM2) is associated with cardiovascular complications and is characterized by high levels of YKL-40, an inflammatory glycoprotein involved in endothelial dysfunction. We investigated the predictive potential of circulating miR-24 in coronary heart diseases (CHD) DM2 patients with CHD, and control subjects. Blood samples were taken from 94 subjects of both genders, and divided over three groups as follows; patients with CHD, patients with DM2 and CHD, and control subjects. Both miR-24 (using real time PCR) and routine parameters were measured. Using bioinformatic analysis and luciferase assays, we found that miR-24 has high complementarity and a high degree of species conservation with respect to the binding sites within the 3′ UTR of the YKL-40 mRNA. The expression levels of circulating miR-24, determined by quantitative real time PCR, were significantly decreased in peripheral blood of DM2-CHD and CHD patients compared with controls. Furthermore, miR-24 strongly associated with DM2-CHD, negatively correlated with YKL-40 in DM2-CHD and DM2 patients after conducting multiple regression analysis. These results provide a novel regulatory mechanism of circulating miR-24 in regulating YKL-40 levels in DM2-CHD, may serve as a biomarker for predicting patients with DM2 and CHD.
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Affiliation(s)
- Xin Deng
- Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China.,Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
| | - Yaofang Liu
- Department of Gynaecology and Obstetrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Mao Luo
- Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China.,Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
| | - Jian Wu
- Medical Research Center, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Rongyue Ma
- The Lee Woo Sing College, Chinese University of Hong Kong, Sha Tin, Hong Kong
| | - Qin Wan
- Department of Endocrinology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Jianbo Wu
- Drug Discovery Research Center, Southwest Medical University, Luzhou, Sichuan, China.,Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China
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Baran A, Myśliwiec H, Szterling-Jaworowska M, Kiluk P, Świderska M, Flisiak I. Serum YKL-40 as a potential biomarker of inflammation in psoriasis. J DERMATOL TREAT 2017; 29:19-23. [PMID: 28498006 DOI: 10.1080/09546634.2017.1330529] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
OBJECTIVE YKL-40 is an inflammatory glycoprotein associated with atherosclerosis, cardiovascular disease, diabetes or metabolic syndrome which are common comorbidities in psoriasis. The aim of the study was to assess serum YKL-40 level in psoriasis and elucidate possible associations with disease activity, inflammatory or metabolic parameters and treatment. METHODS A total of 37 individuals with active plaque-type psoriasis and 15 healthy controls were enrolled. Blood samples were collected before and after 2 weeks of therapy. Serum YKL-40 concentrations were evaluated by enzyme-linked immunosorbent assay (ELISA). The results were correlated with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and topical therapy. RESULTS Median YKL-40 serum levels were significantly increased in psoriatic patients in comparison to the controls (p < .0001). No significant correlations between investigated protein and metabolic parameters as BMI (p = .19), glucose (p = .32) nor lipids levels were found. Significant positive relation with CRP (p = .003) or alanine aminotransferase (p = .04) and no correlation with PASI (p = .2) were noted. Serum YKL-40 level remained unchanged (p = .5) after topical treatment, despite clinical improvement. CONCLUSIONS YKL-40 might be a biomarker of psoriasis and inflammation in psoriatic patients, but not a reliable indicator of metabolic conditions, severity of psoriasis nor efficacy of the treatment.
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Affiliation(s)
- Anna Baran
- a Department of Dermatology and Venereology , Medical University of Bialystok , Bialystok , Poland
| | - Hanna Myśliwiec
- a Department of Dermatology and Venereology , Medical University of Bialystok , Bialystok , Poland
| | | | - Paulina Kiluk
- a Department of Dermatology and Venereology , Medical University of Bialystok , Bialystok , Poland
| | - Magdalena Świderska
- b Department of Infectious Diseases and Hepatology , Medical University of Bialystok , Bialystok , Poland
| | - Iwona Flisiak
- a Department of Dermatology and Venereology , Medical University of Bialystok , Bialystok , Poland
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Glycoprotein YKL-40 Levels in Plasma Are Associated with Fibrotic Changes on HRCT in Asbestos-Exposed Subjects. Mediators Inflamm 2017; 2017:1797512. [PMID: 28588347 PMCID: PMC5446868 DOI: 10.1155/2017/1797512] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2016] [Revised: 04/05/2017] [Accepted: 04/12/2017] [Indexed: 01/28/2023] Open
Abstract
YKL-40 is a chitinase-like glycoprotein produced by alternatively activated macrophages that are associated with wound healing and fibrosis. Asbestosis is a chronic asbestos-induced lung disease, in which injury of epithelial cells and activation of alveolar macrophages lead to enhanced collagen production and fibrosis. We studied if YKL-40 is related to inflammation, fibrosis, and/or lung function in subjects exposed to asbestosis. Venous blood samples were collected from 85 men with moderate or heavy occupational asbestos exposure and from 28 healthy, age-matched controls. Levels of plasma YKL-40, CRP, IL-6, adipsin, and MMP-9 were measured with enzyme-linked immunosorbent assay (ELISA). Plasma YKL-40 levels were significantly higher in subjects with asbestosis (n = 19) than in those with no fibrotic findings in HRCT following asbestos exposure (n = 66) or in unexposed healthy controls. In asbestos-exposed subjects, plasma YKL-40 correlated negatively with lung function capacity parameters FVC (Pearson's r −0.259, p = 0.018) and FEV1 (Pearson's r −0.240, p = 0.028) and positively with CRP (Spearman's rho 0.371, p < 0.001), IL-6 (Spearman's rho 0.314, p = 0.003), adipsin (Spearman's rho 0.459, p < 0.001), and MMP-9 (Spearman's rho 0.243, p = 0.025). The present finding suggests YKL-40 as a biomarker associated with fibrosis and inflammation in asbestos-exposed subjects.
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Roumans NJ, Vink RG, Fazelzadeh P, van Baak MA, Mariman EC. A role for leukocyte integrins and extracellular matrix remodeling of adipose tissue in the risk of weight regain after weight loss. Am J Clin Nutr 2017; 105:1054-1062. [PMID: 28298393 DOI: 10.3945/ajcn.116.148874] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2016] [Accepted: 02/13/2017] [Indexed: 12/16/2022] Open
Abstract
Background: Weight loss (WL) is often followed by weight regain after an energy-restricted dietary intervention (DI). When people are following a diet, the volume of an adipocyte decreases by loss of triglycerides, which creates stress between the cell contents and the surrounding extracellular matrix (ECM). Previously, we observed that genetic variations in ECM genes are associated with an increased risk of weight regain.Objective: We investigated the relation between the expression of ECM genes during WL and a period of weight stabilization (WS) and the risk of weight regain.Design: In this randomized controlled trial, 61 healthy overweight or obese participants followed either a 5-wk very-low-calorie diet (VLCD; 500 kcal/d) or a 12-wk low-calorie diet (1250 kcal/d) (WL period) with a subsequent 4-wk WS period and a 9-mo follow-up. The WL and WS periods combined were considered the DI. Abdominal subcutaneous adipose tissue biopsy samples were collected for microarray analysis. Gene expression changes for a broad set of ECM-related genes were correlated with the weight-regain percentage (WR%).Results: A total of 26 of the 277 genes were significantly correlated with WR% during WL, WS, or the DI periods. Most correlations were observed in the VLCD group during the WS period. Four genes code for leukocyte-specific receptors. These and other genes belong to a group of 26 genes, among which the expression changes were highly correlated (r ≥ 0.7, P ≤ 0.001). This group could be divided into 3 subclusters linking to 2 biological processes-leukocyte integrin gene activity and ECM remodeling-and a link to insulin sensitivity was also apparent.Conclusions: Our present findings indicate the importance of adipose tissue leukocytes for the risk of weight regain. ECM modification also seems to be involved, and we observed a link to insulin sensitivity. This trial was registered at clinicaltrials.gov as NCT01559415.
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Affiliation(s)
- Nadia Jt Roumans
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands; and
| | - Roel G Vink
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands; and
| | - Parastoo Fazelzadeh
- Nutrition, Metabolism, and Genomics Group, Division of Human Nutrition, Wageningen University, Wageningen, Netherlands
| | - Marleen A van Baak
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands; and
| | - Edwin Cm Mariman
- Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, Netherlands; and
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40
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Kzhyshkowska J, Yin S, Liu T, Riabov V, Mitrofanova I. Role of chitinase-like proteins in cancer. Biol Chem 2016; 397:231-47. [PMID: 26733160 DOI: 10.1515/hsz-2015-0269] [Citation(s) in RCA: 91] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Accepted: 12/21/2015] [Indexed: 11/15/2022]
Abstract
Chitinase-like proteins (CLPs) are lectins combining properties of cytokines and growth factors. Human CLPs include YKL-40, YKL-39 and SI-CLP that are secreted by cancer cells, macrophages, neutrophils, synoviocytes, chondrocytes and other cells. The best investigated CLP in cancer is YKL-40. Serum and plasma levels of YKL-40 correlate with poor prognosis in breast, lung, prostate, liver, bladder, colon and other types of cancers. In combination with other circulating factors YKL-40 can be used as a predictive biomarker of cancer outcome. In experimental models YKL-40 supports tumor initiation through binding to RAGE, and is able to induce cancer cell proliferation via ERK1/2-MAPK pathway. YKL-40 supports tumor angiogenesis by interaction with syndecan-1 on endothelial cells and metastatic spread by stimulating production of pro-inflammatory and pro-invasive factors MMP9, CCL2 and CXCL2. CLPs induce production of pro- and anti-inflammatory cytokines and chemokines, and are potential modulators of inflammatory tumor microenvironment. Targeting YKL-40 using neutralizing antibodies exerts anti-cancer effect in preclinical animal models. Multifunctional role of CLPs in regulation of inflammation and intratumoral processes makes them attractive candidates for tumor therapy and immunomodulation. In this review we comprehensively analyze recent data about expression pattern, and involvement of human CLPs in cancer.
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Di Rosa M, Brundo VM, Malaguarnera L. New insights on chitinases immunologic activities. World J Immunol 2016; 6:96-104. [DOI: 10.5411/wji.v6.i2.96] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 10/29/2015] [Accepted: 04/11/2016] [Indexed: 02/05/2023] Open
Abstract
Mammalian chitinases and the related chilectins (ChiLs) belong to the GH18 family, which hydrolyse the glycosidic bond of chitin by a substrate-assisted mechanism. Chitin the fundamental component in the coating of numerous living species is the most abundant natural biopolymer. Mounting evidence suggest that the function of the majority of the mammalian chitinases is not exclusive to catalyze the hydrolysis of chitin producing pathogens, but include crucial role specific in the immunologic activities. The chitinases and chitinase-like proteins are expressed in response to different proinflammatory cues in various tissues by activated macrophages, neutrophils and in different monocyte-derived cell lines. The mechanism and molecular interaction of chitinases in relation to immune regulation embrace bacterial infection, inflammation, dismetabolic and degenerative disease. The aim of this review is to update the reader with regard to the role of chitinases proposed in the recent innate and adaptive immunity literature. The deep scrutiny of this family of enzymes could be a useful base for further studies addressed to the development of potential procedure directing these molecules as diagnostic and prognostic markers for numerous immune and inflammatory diseases.
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Gybel-Brask D, Johansen JS, Christiansen IJ, Skibsted L, Høgdall EVS. Serum YKL-40 and gestational diabetes - an observational cohort study. APMIS 2016; 124:770-5. [PMID: 27457220 DOI: 10.1111/apm.12573] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Accepted: 05/30/2016] [Indexed: 11/27/2022]
Abstract
To examine serum YKL-40 in women developing gestational diabetes mellitus (GDM). In the present large observational cohort study of 1179 pregnant women, we determined serum YKL-40 four times during pregnancy (at gestational age 12, 20, 25, and 32 weeks). Pregnancy outcome was obtained from medical records. Sixty-eight women (5.8%) developed GDM. Serum YKL-40 increased from gestational age (GA) 12 weeks and the following weeks in the women who developed GDM and was independent of BMI, parity, and maternal age (OR = 2.69, 95% CI: 1.45-5.00, p = 0.002). No association was found between serum YKL-40 and the oral glucose tolerance test results. In conclusion, YKL-40 significantly increased in pregnant women with GDM compared with women without GDM, probably reflecting the low-grade inflammation of GDM. However, we did not find an association between serum concentrations of YKL-40 in early pregnancy and the development of GDM and thus we conclude that YKL-40 alone is not usable as a biomarker for early prediction of GDM.
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Affiliation(s)
- Dorte Gybel-Brask
- Department of Obstetrics and Gynecology, Roskilde University Hospital, Roskilde, Denmark.,Molecular Unit, Department of Pathology, Copenhagen University Hospital, Herlev and Gentofte, Denmark
| | - Julia S Johansen
- Department of Medicine and Oncology, Copenhagen University Hospital, Herlev and Gentofte, Denmark.,Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Ib J Christiansen
- Department of Surgical Gastroenterology 360, Hvidovre University Hospital, Copenhagen, Denmark
| | - Lillian Skibsted
- Department of Obstetrics and Gynecology, Roskilde University Hospital, Roskilde, Denmark.,Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Estrid V S Høgdall
- Molecular Unit, Department of Pathology, Copenhagen University Hospital, Herlev and Gentofte, Denmark
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Abstract
Objective: Metabolic syndrome (MS) is defined by a cluster of interdependent physiological, biochemical, and clinical risk factors and linked to a state of chronic inflammation. YKL-40 is known as an inflammatory glycoprotein, which is secreted by various cell lines during inflammation. Thus, we aimed to assess the association of serum YKL-40 levels with the presence and severity of MS. Methods: In this prospective cross-sectional study, a total of 177 consecutive patients [n=114 MS present and n=63 MS absent] were enrolled. MS was defined according to National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. Serum YKL-40 and hs-CRP levels were measured for all participants. Results: Serum YKL-40, hs-CRP and white blood cell count (WBC) were significantly higher in the MS present group (p<0.05). There was a graded relationship between increasing number of MS components and serum YKL-40 level (p<0.05). In addition, serum YKL-40 level was positively correlated with hs-CRP level (r=0.467, p<0.001) and WBC count (r=0.251, p=0.001). In multivariable regression analysis, serum YKL-40 [1.022 (1.011–1.033), p<0.001] and hs-CRP [1.346 (1.111–1.632), p=0.002] were remained as independent predictors for the presence of MS. In the ROC curve analysis, using a cut-off level of 147.0, YKL-40 well predicted the presence of MS with a sensitivity of 73.7% and specificity of 69.8% (AUC: 0.785; 95% CI: 0.718–0.853, p<0.001). Conclusion: In this study, we demonstrated that serum YKL-40 level was significantly associated with the presence of MS. According to these findings, we concluded that serum YKL-40 may be a novel and useful indicator for MS. (Anatol J Cardiol 2016; 16: 953-8)
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Wesolowska-Andersen A, Seibold MA. Is the Road to Precision Medicine in Chronic Lung Disease Paved with Degraded Chitin? Am J Respir Crit Care Med 2016; 193:107-8. [PMID: 26771411 DOI: 10.1164/rccm.201510-1925ed] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Affiliation(s)
| | - Max A Seibold
- 1 Center for Genes, Environment, and Health National Jewish Health Denver, Colorado and.,2 Department of Pediatrics National Jewish Health Denver, Colorado
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Di Rosa M, Malaguarnera L. Chitinase 3 Like-1: An Emerging Molecule Involved in Diabetes and Diabetic Complications. Pathobiology 2016; 83:228-242. [PMID: 27189062 DOI: 10.1159/000444855] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Accepted: 02/18/2016] [Indexed: 01/05/2025] Open
Abstract
Chitinase 3 like-1 (CHI3L1) is a chitinase-like protein member of family 18 chitinases, expressed in innate immune cells and involved in endothelial dysfunction and tissue remodelling. Since CHI3L1 is highly expressed in a variety of inflammatory diseases of infectious and non-infectious aetiology, it is recognised as a non-invasive prognostic biomarker for inflammation. A variety of studies revealing the increase in CHI3L1 levels in obesity, insulin resistance and in pathological conditions, such as atherosclerosis, coronary artery disease, acute ischaemic stroke, nephropathy, diabetic retinopathy and osteolytic processes, have suggested that CHI3L1 may also play a critical role in the evolution and complication of diabetes mellitus (DM). In this review we highlight the impact of CHI3L1 expression in DM and its contribution to the complication of this disease.
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Affiliation(s)
- Michelino Di Rosa
- Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, Catania, Italy
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Görgens SW, Hjorth M, Eckardt K, Wichert S, Norheim F, Holen T, Lee S, Langleite T, Birkeland KI, Stadheim HK, Kolnes KJ, Tangen DS, Kolnes AJ, Jensen J, Drevon CA, Eckel J. The exercise-regulated myokine chitinase-3-like protein 1 stimulates human myocyte proliferation. Acta Physiol (Oxf) 2016; 216:330-45. [PMID: 26303257 DOI: 10.1111/apha.12579] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2015] [Revised: 06/22/2015] [Accepted: 08/15/2015] [Indexed: 01/10/2023]
Abstract
AIM Chitinase-3-like protein 1 (CHI3L1) is involved in tissue remodelling and inflammatory processes. Plasma levels are elevated in patients with insulin resistance and T2DM. We recently showed that CHI3L1 and its receptor protease-activated receptor 2 (PAR-2) are expressed in skeletal muscle. Activation of PAR-2 by CHI3L1 protects against TNF-α-induced inflammation and insulin resistance. However, the effect of exercise on CHI3L1 and PAR-2 signalling remains unknown. The aim of this work was to study the impact of exercise on CHI3L1 production and the effect of CHI3L1/PAR-2 signalling on skeletal muscle growth and repair. METHODS Three human exercise studies were used to measure CHI3L1 plasma levels (n = 32). In addition, muscle and adipose tissue CHI3L1 mRNA expression was measured in response to acute and long-term exercise (n = 24). Primary human skeletal muscle cells were differentiated in vitro, and electrical pulse stimulation was applied. In addition, myoblasts were incubated with CHI3L1 protein and activation of MAP kinase signalling as well as proliferation was measured. RESULTS Circulating CHI3L1 levels and muscle CHI3L1 mRNA were increased after acute exercise. In addition, CHI3L1 mRNA expression as well as CHI3L1 secretion was enhanced in electrically stimulated cultured myotubes. Incubation of cultured human myoblasts with CHI3L1 protein leads to a strong activation of p44/42, p38 MAPK and Akt as well as enhanced myoblast proliferation. CONCLUSION Our findings suggest that CHI3L1 is induced by acute exercise and that CHI3L1/PAR-2 signalling activates myocyte proliferation, which is important for restructuring of skeletal muscle in the response to exercise training.
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Affiliation(s)
- S. W. Görgens
- Paul-Langerhans-Group for Integrative Physiology; German Diabetes Center (DDZ); Düsseldorf Germany
| | - M. Hjorth
- Department of Nutrition; Faculty of Medicine; Institute of Basic Medical Sciences; University of Oslo; Oslo Norway
| | - K. Eckardt
- Paul-Langerhans-Group for Integrative Physiology; German Diabetes Center (DDZ); Düsseldorf Germany
- Department of Nutrition; Faculty of Medicine; Institute of Basic Medical Sciences; University of Oslo; Oslo Norway
| | - S. Wichert
- Paul-Langerhans-Group for Integrative Physiology; German Diabetes Center (DDZ); Düsseldorf Germany
| | - F. Norheim
- Department of Nutrition; Faculty of Medicine; Institute of Basic Medical Sciences; University of Oslo; Oslo Norway
| | - T. Holen
- Department of Nutrition; Faculty of Medicine; Institute of Basic Medical Sciences; University of Oslo; Oslo Norway
| | - S. Lee
- Department of Nutrition; Faculty of Medicine; Institute of Basic Medical Sciences; University of Oslo; Oslo Norway
| | - T. Langleite
- Department of Nutrition; Faculty of Medicine; Institute of Basic Medical Sciences; University of Oslo; Oslo Norway
| | - K. I. Birkeland
- Department of Nutrition; Faculty of Medicine; Institute of Basic Medical Sciences; University of Oslo; Oslo Norway
| | - H. K. Stadheim
- Department of Physical Performance; Norwegian School of Sport Sciences; Oslo Norway
| | - K. J. Kolnes
- Charles University Third Faculty of Medicine; Prague Czech Republic
| | - D. S. Tangen
- Department of Physical Performance; Norwegian School of Sport Sciences; Oslo Norway
| | - A. J. Kolnes
- Charles University Third Faculty of Medicine; Prague Czech Republic
| | - J. Jensen
- Department of Physical Performance; Norwegian School of Sport Sciences; Oslo Norway
| | - C. A. Drevon
- Department of Nutrition; Faculty of Medicine; Institute of Basic Medical Sciences; University of Oslo; Oslo Norway
| | - J. Eckel
- Paul-Langerhans-Group for Integrative Physiology; German Diabetes Center (DDZ); Düsseldorf Germany
- German Center for Diabetes Research (DZD e.V.); Düsseldorf Germany
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Abstract
OBJECTIVE Serum YKL-40 levels are elevated in patients with type 1 and 2 diabetes. However, the correlation between YKL-40 and gestational diabetes mellitus (GDM) remains unknown. The present study compared serum YKL-40 levels in pregnant women with GDM and those with normal glucose tolerance and evaluated the relationship between YKL-40 and insulin-resistant syndrome. METHODS Thirty-five patients with GDM and 43 age-matched healthy pregnant women at 24-28 weeks of gestation were studied. In addition to anthropometric assessments, serum glucose, insulin, YKL-40, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein and glycated hemoglobin were measured in all subjects. All subjects underwent a 2-h 75-g oral glucose tolerance test (OGTT). Body mass index (BMI) and the homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. RESULTS Fasting and 2 h serum YKL-40 levels were significantly higher in pregnant women with GDM compared with controls (77.3 ± 29.3 versus 50.9 ± 16.7 ng/mL, p < 0.001, fasting concentrations; 63.5 ± 20.1 versus 40.6 ± 10.7 ng/mL, p = 0.009, 2 h concentrations). OGTT had no effect on YKL-40 levels in either group (p > 0.05). There were significant correlations between YKL-40 and glycated hemoglobin (β = 0.37, p = 0.006), fasting insulin (β = 0.49, p = 0.001) and HOMA-IR (β = 0.18, p = 0.015) in the GDM group. CONCLUSIONS Serum YKL-40 levels are elevated in patients with GDM but are unaffected by OGTT. YKL-40 levels are related to glycated hemoglobin, fasting insulin and HOMA-IR. These results suggest that YKL-40 may be a major contributor to GDM.
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Affiliation(s)
- Jian Li
- a Department of Endocrinology , Shandong Provincial Hospital Affiliated to Shandong University, Shandong Clinical Medical Center of Endocrinology and Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine , 324 Jing 5 Rd , Jinan , Shandong , P.R. China
- b Department of Endocrinology , Liaocheng People's Hospital , 67 Dongchang Xi Rd , Liaocheng , Shandong , P.R. China , and
| | - Guifen Niu
- b Department of Endocrinology , Liaocheng People's Hospital , 67 Dongchang Xi Rd , Liaocheng , Shandong , P.R. China , and
| | - Huaiguo Wang
- c Department of Nephrology , Liaocheng People's Hospital , 67 Dongchang Xi Rd , Liaocheng , Shandong , P.R. China
| | - Kun Wang
- b Department of Endocrinology , Liaocheng People's Hospital , 67 Dongchang Xi Rd , Liaocheng , Shandong , P.R. China , and
| | - Bingtong Huang
- b Department of Endocrinology , Liaocheng People's Hospital , 67 Dongchang Xi Rd , Liaocheng , Shandong , P.R. China , and
| | - Minglong Li
- a Department of Endocrinology , Shandong Provincial Hospital Affiliated to Shandong University, Shandong Clinical Medical Center of Endocrinology and Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine , 324 Jing 5 Rd , Jinan , Shandong , P.R. China
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Rodríguez A, Ezquerro S, Méndez-Giménez L, Becerril S, Frühbeck G. Revisiting the adipocyte: a model for integration of cytokine signaling in the regulation of energy metabolism. Am J Physiol Endocrinol Metab 2015; 309:E691-714. [PMID: 26330344 DOI: 10.1152/ajpendo.00297.2015] [Citation(s) in RCA: 190] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Accepted: 08/24/2015] [Indexed: 02/08/2023]
Abstract
Adipose tissue constitutes an extremely active endocrine organ with a network of signaling pathways enabling the organism to adapt to a wide range of different metabolic challenges, such as starvation, stress, infection, and short periods of gross energy excess. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a huge variety of hormones, cytokines, complement and growth factors, extracellular matrix proteins, and vasoactive factors, collectively termed adipokines. Obesity is associated with adipose tissue dysfunction leading to the onset of several pathologies including type 2 diabetes, dyslipidemia, nonalcoholic fatty liver, or hypertension, among others. The mechanisms underlying the development of obesity and its associated comorbidities include the hypertrophy and/or hyperplasia of adipocytes, adipose tissue inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. Recently, the potential role of brown and beige adipose tissue in the protection against obesity has been also recognized. In contrast to white adipocytes, which store energy in the form of fat, brown and beige fat cells display energy-dissipating capacity through the promotion of triacylglycerol clearance, glucose disposal, and generation of heat for thermogenesis. Identification of the morphological and molecular changes in white, beige, and brown adipose tissue during weight gain is of utmost relevance for the identification of pharmacological targets for the treatment of obesity and its associated metabolic diseases.
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Affiliation(s)
- Amaia Rodríguez
- Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; and Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain
| | - Silvia Ezquerro
- Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain
| | - Leire Méndez-Giménez
- Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; and Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain
| | - Sara Becerril
- Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; and Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain
| | - Gema Frühbeck
- Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain; Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; and Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain
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CHI3L1 nuclear localization in monocyte derived dendritic cells. Immunobiology 2015; 221:347-56. [PMID: 26466985 DOI: 10.1016/j.imbio.2015.09.023] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Revised: 09/03/2015] [Accepted: 09/30/2015] [Indexed: 02/07/2023]
Abstract
Chitinase-3-like-1 protein (CHI3L1) is a glycosyl hydrolase (GH) highly expressed in a variety of inflammatory diseases at infectious and non-infectious etiology. CHI3L1 is produced by a wide variety of cells including monocyte-derived macrophages cell lines such as polarized M1 and M2 type macrophages, osteoclasts and Kupffer cells. In this study we have examined the expression of CHI3L1 during the differentiation and maturation of dendritic cells. Magnetically-isolated peripheral blood monocytes were differentiated toward immature DCs (iDC) and mature DCs (mDCs) through a combination of factors and cytokines. Our result showed, for the first time, that CHI3L1 is expressed during the process of differentiation and maturation of dendritic cells in time dependent manner. Furthermore, the CHI3L1 is evenly distributed in cytoplasm and in the nucleus of both the iDCs and mDCs. These results suggest that CHI3L1 may play crucial role in the DCs immunoresponse.
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Abstract
OBJECTIVES There is accumulating evidence that inflammation plays a major role in the development of the slow coronary flow (SCF) phenomenon. YKL-40 has been suggested to be a potential biomarker of inflammation. In this study, we aimed to study YKL-40 as it relates to SCF. MATERIALS AND METHODS Patients who underwent coronary angiography before and had angiographically normal coronary arteries of varying coronary flow rates without any atherosclerotic lesion were enrolled in this study. Patients who had thrombolysis in myocardial infarction frame counts (TFC) above the normal cutoffs were considered to have SCF and those within normal limits were considered to have normal coronary flow (NCF). The YKL-40 levels and biochemical profiles of all patients were studied and analyzed. RESULTS There were 41 patients in the SCF group and 209 patients in the NCF group. Compared with the NCF patients, SCF patients had higher serum high-sensitivity C-reactive protein (hs-CRP) (P=0.0003) and YKL-40 (P=0.0007) levels. A positive correlation was detected between the YKL-40 levels and hs-CRP (r=0.7021, P<0.001), and the mean TFC (r=0.4038, P=0.0088) in SCF patients. CONCLUSION Our study showed that YKL-40 levels are higher and correlated positively with TFC and hs-CRP in SCF patients. This finding suggests that YKL-40 may be a useful marker and predictor for SCF.
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