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Gaál Z, Fodor J, Oláh T, Szabó IG, Balatoni I, Csernoch L. Implication of microRNAs as messengers of exercise adaptation in junior female triathlonists. Sci Rep 2024; 14:22858. [PMID: 39354034 PMCID: PMC11445571 DOI: 10.1038/s41598-024-73670-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2023] [Accepted: 09/19/2024] [Indexed: 10/03/2024] Open
Abstract
While expression profile of muscle-specific miRNAs following endurance training is well-characterized, information about exercise-induced changes of metabolism-regulating miRNAs is limited, especially in female and junior athletes. Major aim of this study was to examine a set of miRNAs related to mitochondrial function and metabolism in highly professional junior female athletes. The Hungarian National Junior Triathlon Team (n = 4), completed standardized running and cycling sessions. Expression levels of miR-133a, miR-210, miR-494 and miR-127-3p were determined by RT-qPCR in whole blood and serum samples, withdrawn directly before, and after the exercise, and 24 and 48 h later. The expression of miR-494, miR-127-3p and miR-210 showed strong correlation with each other. In serum, nearly significant increment of miR-127-3p levels was detected, that may be a novel biomarker of exercise adaptation. Its expression was significantly higher than that of miR-210. In whole blood, significantly higher miR-210 than miR-494 and miR-127-3p levels were observed. MiRNA expression profile of the youngest athlete was markedly different compared to others. Our results suggest that miRNAs related to mitochondrial function and metabolism are involved in exercise adaptation. The present study may facilitate further research with larger potential participant pools, contributing to improved prevention and treatment of chronic diseases of civilization.
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Affiliation(s)
- Zsuzsanna Gaál
- Institute of Pediatrics, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
| | - János Fodor
- Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei Körút 98, Debrecen, 4032, Hungary
| | - Tamás Oláh
- Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei Körút 98, Debrecen, 4032, Hungary
| | - Ivett Gabriella Szabó
- Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei Körút 98, Debrecen, 4032, Hungary
- Doctoral School of Molecular Medicine, University of Debrecen, Debrecen, 4032, Hungary
| | | | - László Csernoch
- Department of Physiology, Faculty of Medicine, University of Debrecen, Nagyerdei Körút 98, Debrecen, 4032, Hungary.
- HUN-REN-DE Cell Physiology Research Group, University of Debrecen, Debrecen, 4032, Hungary.
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Lizárraga D, Gómez-Gil B, García-Gasca T, Ávalos-Soriano A, Casarini L, Salazar-Oroz A, García-Gasca A. Gestational diabetes mellitus: genetic factors, epigenetic alterations, and microbial composition. Acta Diabetol 2024; 61:1-17. [PMID: 37660305 DOI: 10.1007/s00592-023-02176-y] [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: 06/07/2023] [Accepted: 08/18/2023] [Indexed: 09/05/2023]
Abstract
Gestational diabetes mellitus (GDM) is a common metabolic disorder, usually diagnosed during the third trimester of pregnancy that usually disappears after delivery. In GDM, the excess of glucose, fatty acids, and amino acids results in foetuses large for gestational age. Hyperglycaemia and insulin resistance accelerate the metabolism, raising the oxygen demand, and creating chronic hypoxia and inflammation. Women who experienced GDM and their offspring are at risk of developing type-2 diabetes, obesity, and other metabolic or cardiovascular conditions later in life. Genetic factors may predispose the development of GDM; however, they do not account for all GDM cases; lifestyle and diet also play important roles in GDM development by modulating epigenetic signatures and the body's microbial composition; therefore, this is a condition with a complex, multifactorial aetiology. In this context, we revised published reports describing GDM-associated single-nucleotide polymorphisms (SNPs), DNA methylation and microRNA expression in different tissues (such as placenta, umbilical cord, adipose tissue, and peripheral blood), and microbial composition in the gut, oral cavity, and vagina from pregnant women with GDM, as well as the bacterial composition of the offspring. Altogether, these reports indicate that a number of SNPs are associated to GDM phenotypes and may predispose the development of the disease. However, extrinsic factors (lifestyle, nutrition) modulate, through epigenetic mechanisms, the risk of developing the disease, and some association exists between the microbial composition with GDM in an organ-specific manner. Genes, epigenetic signatures, and microbiota could be transferred to the offspring, increasing the possibility of developing chronic degenerative conditions through postnatal life.
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Affiliation(s)
- Dennise Lizárraga
- Laboratory of Molecular and Cell Biology, Centro de Investigación en Alimentación y Desarrollo, Avenida Sábalo Cerritos s/n, 82112, Mazatlán, Sinaloa, Mexico
| | - Bruno Gómez-Gil
- Laboratory of Microbial Genomics, Centro de Investigación en Alimentación y Desarrollo, Avenida Sábalo Cerritos s/n, 82112, Mazatlán, Sinaloa, Mexico
| | - Teresa García-Gasca
- Laboratory of Molecular and Cellular Biology, Facultad de Ciencias Naturales, Universidad Autónoma de Querétaro, Avenida de las Ciencias s/n, 76230, Juriquilla, Querétaro, Mexico
| | - Anaguiven Ávalos-Soriano
- Laboratory of Molecular and Cell Biology, Centro de Investigación en Alimentación y Desarrollo, Avenida Sábalo Cerritos s/n, 82112, Mazatlán, Sinaloa, Mexico
| | - Livio Casarini
- Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, via G. Campi 287, 41125, Modena, Italy
| | - Azucena Salazar-Oroz
- Maternal-Fetal Department, Instituto Vidalia, Hospital Sharp Mazatlán, Avenida Rafael Buelna y Dr. Jesús Kumate s/n, 82126, Mazatlán, Sinaloa, Mexico
| | - Alejandra García-Gasca
- Laboratory of Molecular and Cell Biology, Centro de Investigación en Alimentación y Desarrollo, Avenida Sábalo Cerritos s/n, 82112, Mazatlán, Sinaloa, Mexico.
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Elhag DA, Al Khodor S. Exploring the potential of microRNA as a diagnostic tool for gestational diabetes. J Transl Med 2023; 21:392. [PMID: 37330548 PMCID: PMC10276491 DOI: 10.1186/s12967-023-04269-2] [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: 04/26/2023] [Accepted: 06/11/2023] [Indexed: 06/19/2023] Open
Abstract
MicroRNAs (miRNAs) are small non-coding RNAs that play critical roles in regulating host gene expression. Recent studies have indicated a role of miRNAs in the pathogenesis of gestational diabetes mellitus (GDM), a common pregnancy-related disorder characterized by impaired glucose metabolism. Aberrant expression of miRNAs has been observed in the placenta and/or maternal blood of GDM patients, suggesting their potential use as biomarkers for early diagnosis and prognosis. Additionally, several miRNAs have been shown to modulate key signaling pathways involved in glucose homeostasis, insulin sensitivity, and inflammation, providing insights into the pathophysiology of GDM. This review summarizes the current knowledge on the dynamics of miRNA in pregnancy, their role in GDM as well as their potential as diagnostic and therapeutic targets.
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Affiliation(s)
- Duaa Ahmed Elhag
- Maternal and Child Health Division, Research Branch, Sidra Medicine, Doha, Qatar
| | - Souhaila Al Khodor
- Maternal and Child Health Division, Research Branch, Sidra Medicine, Doha, Qatar.
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Goyal S, Rani J, Bhat MA, Vanita V. Genetics of diabetes. World J Diabetes 2023; 14:656-679. [PMID: 37383588 PMCID: PMC10294065 DOI: 10.4239/wjd.v14.i6.656] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 03/13/2023] [Accepted: 04/17/2023] [Indexed: 06/14/2023] Open
Abstract
Diabetes mellitus is a complicated disease characterized by a complex interplay of genetic, epigenetic, and environmental variables. It is one of the world's fastest-growing diseases, with 783 million adults expected to be affected by 2045. Devastating macrovascular consequences (cerebrovascular disease, cardiovascular disease, and peripheral vascular disease) and microvascular complications (like retinopathy, nephropathy, and neuropathy) increase mortality, blindness, kidney failure, and overall quality of life in individuals with diabetes. Clinical risk factors and glycemic management alone cannot predict the development of vascular problems; multiple genetic investigations have revealed a clear hereditary component to both diabetes and its related complications. In the twenty-first century, technological advancements (genome-wide association studies, next-generation sequencing, and exome-sequencing) have led to the identification of genetic variants associated with diabetes, however, these variants can only explain a small proportion of the total heritability of the condition. In this review, we address some of the likely explanations for this "missing heritability", for diabetes such as the significance of uncommon variants, gene-environment interactions, and epigenetics. Current discoveries clinical value, management of diabetes, and future research directions are also discussed.
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Affiliation(s)
- Shiwali Goyal
- Department of Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Rockville, MD 20852, United States
| | - Jyoti Rani
- Department of Human Genetics, Guru Nanak Dev University, Amritsar 143005, Punjab, India
| | - Mohd Akbar Bhat
- Department of Ophthalmology, Georgetown University Medical Center, Washington DC, DC 20057, United States
| | - Vanita Vanita
- Department of Human Genetics, Guru Nanak Dev University, Amritsar 143005, Punjab, India
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Stevanović-Silva J, Beleza J, Coxito P, Oliveira PJ, Ascensão A, Magalhães J. Gestational Exercise Antagonises the Impact of Maternal High-Fat High-Sucrose Diet on Liver Mitochondrial Alterations and Quality Control Signalling in Male Offspring. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:1388. [PMID: 36674144 PMCID: PMC9858977 DOI: 10.3390/ijerph20021388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 01/03/2023] [Accepted: 01/09/2023] [Indexed: 06/17/2023]
Abstract
Maternal high-caloric nutrition and related gestational diabetes mellitus (GDM) are relevant modulators of the intrauterine environment, increasing the risk of liver metabolic alterations in mothers and offspring. In contrast, as a non-pharmacological approach against metabolic disorders, exercise is highly recommended in GDM treatment. We analysed whether gestational exercise (GE) protects mothers from diet-induced GDM metabolic consequences and mitigates liver mitochondrial deleterious alterations in their 6-week-old male offspring. Female Sprague Dawley rats were fed with control or high-fat high-sucrose (HFHS) diet and kept sedentary or submitted to GE. Male offspring were sedentary and fed with control diet. Sedentary HFHS mothers and their offspring showed impaired hepatic mitochondrial biogenesis and morphological evidence of mitochondrial remodelling. In contrast, GE-related beneficial effects were demonstrated by upregulation of mitochondrial biogenesis signalling markers and mitochondrial fusion proteins and downregulation of mitochondrial fission protein. Alterations in miR-34a, miR-130b, and miR-494, associated with epigenetic regulation of mitochondrial biogenesis, suggested that GE is a more critical modulator of intergenerational changes in miRs expression than the maternal diet. Our data showed that GE positively modulated the altered hepatic mitochondrial biogenesis and dynamics markers and quality control signalling associated with maternal HFHS-diet-related GDM in mothers and offspring.
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Affiliation(s)
- Jelena Stevanović-Silva
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, 4200-450 Porto, Portugal
| | - Jorge Beleza
- Department of Cell Biology, Physiology & Immunology, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain
| | - Pedro Coxito
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, 4200-450 Porto, Portugal
| | - Paulo J. Oliveira
- CNC—Center for Neuroscience and Cell Biology, CIBB—Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal
| | - António Ascensão
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, 4200-450 Porto, Portugal
| | - José Magalhães
- Laboratory of Metabolism and Exercise (LaMetEx), Research Centre in Physical Activity, Health and Leisure (CIAFEL), Laboratory for Integrative and Translational Research in Population Health (ITR), Faculty of Sport, University of Porto, 4200-450 Porto, Portugal
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Masete M, Dias S, Malaza N, Adam S, Pheiffer C. A Big Role for microRNAs in Gestational Diabetes Mellitus. Front Endocrinol (Lausanne) 2022; 13:892587. [PMID: 35957839 PMCID: PMC9357936 DOI: 10.3389/fendo.2022.892587] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 06/24/2022] [Indexed: 12/16/2022] Open
Abstract
Maternal diabetes is associated with pregnancy complications and poses a serious health risk to both mother and child. Growing evidence suggests that pregnancy complications are more frequent and severe in pregnant women with pregestational type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) compared to women with gestational diabetes mellitus (GDM). Elucidating the pathophysiological mechanisms that underlie the different types of maternal diabetes may lead to targeted strategies to prevent or reduce pregnancy complications. In recent years, microRNAs (miRNAs), one of the most common epigenetic mechanisms, have emerged as key players in the pathophysiology of pregnancy-related disorders including diabetes. This review aims to provide an update on the status of miRNA profiling in pregnancies complicated by maternal diabetes. Four databases, Pubmed, Web of Science, EBSCOhost, and Scopus were searched to identify studies that profiled miRNAs during maternal diabetes. A total of 1800 articles were identified, of which 53 are included in this review. All studies profiled miRNAs during GDM, with no studies on miRNA profiling during pregestational T1DM and T2DM identified. Studies on GDM were mainly focused on the potential of miRNAs to serve as predictive or diagnostic biomarkers. This review highlights the lack of miRNA profiling in pregnancies complicated by T1DM and T2DM and identifies the need for miRNA profiling in all types of maternal diabetes. Such studies could contribute to our understanding of the mechanisms that link maternal diabetes type with pregnancy complications.
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Affiliation(s)
- Matladi Masete
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa
- Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | - Stephanie Dias
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa
| | - Nompumelelo Malaza
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa
- Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | - Sumaiya Adam
- Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
| | - Carmen Pheiffer
- Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa
- Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
- Center for Cardio-Metabolic Research in Africa (CARMA), Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Cape Town, South Africa
- *Correspondence: Carmen Pheiffer,
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7
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Zhang TN, Wang W, Huang XM, Gao SY. Non-Coding RNAs and Extracellular Vehicles: Their Role in the Pathogenesis of Gestational Diabetes Mellitus. Front Endocrinol (Lausanne) 2021; 12:664287. [PMID: 34093439 PMCID: PMC8173208 DOI: 10.3389/fendo.2021.664287] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 05/06/2021] [Indexed: 12/21/2022] Open
Abstract
Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset or first recognition in the second or third trimester of pregnancy. GDM has a considerable impact on health outcomes of the mother and offspring during pregnancy, delivery, and beyond. Although the exact mechanism regarding GDM remains unclear, numerous studies have suggested that non-coding RNAs, including long non-coding (lnc)RNAs, microRNAs, and circular RNAs, were involved in the pathogenesis of GDM in which they played vital regulatory roles. Additionally, several studies have revealed that extracellular vehicles also participated in the pathogenesis of GDM, highlighting their important role in this disease. Considering the lack of effective biomarkers for the early identification of and specific treatment for GDM, non-coding RNAs and extracellular vehicles may be promising biomarkers and even targets for GDM therapies. This review provides an update on our understanding of the role of non-coding RNAs and extracellular vehicles in GDM. As our understanding of the function of lncRNAs and extracellular vehicles improves, the future appears promising for their use as potential biomarkers and treatment targets for GDM in clinical practice.
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Affiliation(s)
- Tie-Ning Zhang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Wei Wang
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xin-Mei Huang
- Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
- *Correspondence: Xin-Mei Huang, ; Shan-Yan Gao,
| | - Shan-Yan Gao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
- Clinical Research Center, Shengjing Hospital of China Medical University, Shenyang, China
- *Correspondence: Xin-Mei Huang, ; Shan-Yan Gao,
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Liu ZN, Jiang Y, Liu XQ, Yang MM, Chen C, Zhao BH, Huang HF, Luo Q. MiRNAs in Gestational Diabetes Mellitus: Potential Mechanisms and Clinical Applications. J Diabetes Res 2021; 2021:4632745. [PMID: 34869778 PMCID: PMC8635917 DOI: 10.1155/2021/4632745] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 06/08/2021] [Accepted: 10/19/2021] [Indexed: 12/12/2022] Open
Abstract
Gestational diabetes mellitus (GDM) is a common pregnancy complication which is normally diagnosed in the second trimester of gestation. With an increasing incidence, GDM poses a significant threat to maternal and offspring health. Therefore, we need a deeper understanding of GDM pathophysiology and novel investigation on the diagnosis and treatment for GDM. MicroRNAs (miRNAs), a class of endogenic small noncoding RNAs with a length of approximately 19-24 nucleotides, have been reported to exert their function in gene expression by binding to proteins or being enclosed in membranous vesicles, such as exosomes. Studies have investigated the roles of miRNAs in the pathophysiological mechanism of GDM and their potential as noninvasive biological candidates for the management of GDM, including diagnosis and treatment. This review is aimed at summarizing the pathophysiological significance of miRNAs in GDM development and their potential function in GDM clinical diagnosis and therapeutic approach. In this review, we summarized an integrated expressional profile and the pathophysiological significance of placental exosomes and associated miRNAs, as well as other plasma miRNAs such as exo-AT. Furthermore, we also discussed the practical application of exosomes in GDM postpartum outcomes and the potential function of several miRNAs as therapeutic target in the GDM pathological pathway, thus providing a novel clinical insight of these biological signatures into GDM therapeutic approach.
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Affiliation(s)
- Zhao-Nan Liu
- Department of Reproductive Genetics, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China
| | - Ying Jiang
- Department of Obstetrics, Women's Hospital, School of Medicine, Zhejiang University, China
| | - Xuan-Qi Liu
- Department of Reproductive Genetics, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China
| | - Meng-Meng Yang
- Department of Obstetrics, Women's Hospital, School of Medicine, Zhejiang University, China
| | - Cheng Chen
- Department of Obstetrics, Women's Hospital, School of Medicine, Zhejiang University, China
| | - Bai-Hui Zhao
- Department of Obstetrics, Women's Hospital, School of Medicine, Zhejiang University, China
| | - He-Feng Huang
- Department of Reproductive Genetics, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China
| | - Qiong Luo
- Department of Obstetrics, Women's Hospital, School of Medicine, Zhejiang University, China
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Zhang H, Wang Q, Yang K, Zheng H, Hu Y. Effects of miR-22-3p targeted regulation of Socs3 on the hepatic insulin resistance in mice with gestational diabetes mellitus. Am J Transl Res 2020; 12:7287-7296. [PMID: 33312367 PMCID: PMC7724336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 09/28/2020] [Indexed: 06/12/2023]
Abstract
OBJECTIVE Gestational diabetes mellitus (GDM) is one of the common complications of pregnant women, with serious threatening to pregnant women and newborns. The pathogenesis of GDM remains unclear now. This study aims to explore the effects of miR-22-3p targeted regulation of suppressors of cytokine signaling 3 (Socs3) on the hepatic insulin resistance (HIR) in mice with GDM. METHODS Healthy SPF C57BL/6J mice were selected to establish GDM model and divided into 7 groups: Normal group, Model group, NC-(negative control) mimic group, miR-22-3p mimic group, NC-pcDNA3.0 group, pcDNA3.0-Socs3 group, and miR-22-3p mimic + pcDNA3.0-Socs3 group. The islet morphology, and the expressions of miR-22-3p, Socs3 mRNA and Socs3 protein in the islet tissues were detected by HE staining, qRT-PCR and Western blot. Fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) were measured. Oral glucose tolerance test (OGTT) was performed to detect FBG and fasting insulin (FINS) contents, and insulin resistance (HOMA-IR) was calculated. RESULTS Compared with the Normal group, the model group had decreased levels of miR-22-3p and HDL-C, while increased levels of Socs3 mRNA and protein expressions, OGTT, FBG, FINS, and HOMA-IR, TG and TC (all P < 0.05). Compared with the Model group, the above indicators (OGTT, FBG, FINS, HOMA-IR, TG, TC and HDL-C) were improved in the miR-22-3p mimic group, but worsened in the pcDNA3.0-Socs3 group (all P < 0.05). CONCLUSION miR-22-3p can down-regulate the expression of Socs3, thereby inhibiting HIR in GDM mice.
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Affiliation(s)
- Huan Zhang
- Department of Emergency, The Fourth Hospital of ShijiazhuangShijiazhuang, Hebei Province, China
| | - Qiaoyi Wang
- Department of Emergency, Weifang Traditional Chinese Medicine HospitalWeifang, Shandong Province, China
| | - Kun Yang
- The First Department of Obstetrics, Liaocheng Second People’s HospitalLiaocheng, Shandong Province, China
| | - Hanjing Zheng
- Department of Emergency, The Fourth Hospital of ShijiazhuangShijiazhuang, Hebei Province, China
| | - Yujing Hu
- The Third Department of Obstetrics, The People’s Hospital of Pingyi CountyLinyi, Shandong Province, China
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Tu C, Wang L, Tao H, Gu L, Zhu S, Chen X. Expression of miR-409-5p in gestational diabetes mellitus and its relationship with insulin resistance. Exp Ther Med 2020; 20:3324-3329. [PMID: 32855704 PMCID: PMC7444361 DOI: 10.3892/etm.2020.9049] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Accepted: 06/19/2020] [Indexed: 12/12/2022] Open
Abstract
Expression of miR-409-5p in gestational diabetes mellitus (GDM) and its relationship with insulin resistance were explore. One hundred and forty-nine pregnant women who underwent antenatal examination in Taizhou First People's Hospital were divided into a GDM group and a control group according to whether they had GDM or not. Serum miR-409-5p expression of the two groups was detected, and the levels of glycosylated hemoglobin (HbAlc) and other GDM-related biochemical indicators were measured. Fasting plasma glucose (FPG) was determined by glucose oxidase method, fasting insulin (FINS) was detected by radioimmunoassay, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The relationship between miR-409-5p and other biochemical indicators and insulin resistance was analyzed, and logistic multivariate regression was employed to analyze the risk factors of GDM. miR-409-5p was highly expressed in the serum of GDM patients. HbAlc, FPG, FINS, and HOMA-IR in pregnant women in the GDM group were markedly higher than those in the control group. The serum miR-409-5p in GDM pregnant women showed a positive correlation with HbAlc, FPG, FINS, and HOMA-IR (P<0.05). The insulin resistance group presented remarkably higher serum miR-409-5p level than the non-insulin resistance group. Moreover, it was found that elevated miR-409-5p, FINS, and HOMA-IR were all independent risk factors for the onset of GDM. miR-409-5p is highly expressed in the serum of patients with GDM, and it is positively correlated with insulin resistance index of GDM patients, which may be a potential target for clinical diagnosis and treatment of GDM.
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Affiliation(s)
- Chuanfa Tu
- Department of Endocrinology, Taizhou First People's Hospital, Taizhou, Zhejiang 318020, P.R. China
| | - Lijun Wang
- Department of Endocrinology, Taizhou First People's Hospital, Taizhou, Zhejiang 318020, P.R. China
| | - Haiying Tao
- Department of Endocrinology, Taizhou First People's Hospital, Taizhou, Zhejiang 318020, P.R. China
| | - Lingjia Gu
- Department of Endocrinology, Taizhou First People's Hospital, Taizhou, Zhejiang 318020, P.R. China
| | - Shuang Zhu
- Department of Endocrinology, Taizhou First People's Hospital, Taizhou, Zhejiang 318020, P.R. China
| | - Xiaolu Chen
- Department of Obstetrics and Gynecology, Taizhou First People's Hospital, Taizhou, Zhejiang 318020, P.R. China
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Substantially Altered Expression Profile of Diabetes/Cardiovascular/Cerebrovascular Disease Associated microRNAs in Children Descending from Pregnancy Complicated by Gestational Diabetes Mellitus-One of Several Possible Reasons for an Increased Cardiovascular Risk. Cells 2020; 9:cells9061557. [PMID: 32604801 PMCID: PMC7349356 DOI: 10.3390/cells9061557] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2020] [Revised: 06/19/2020] [Accepted: 06/25/2020] [Indexed: 12/14/2022] Open
Abstract
Gestational diabetes mellitus (GDM), one of the major pregnancy-related complications, characterized as a transitory form of diabetes induced by insulin resistance accompanied by a low/absent pancreatic beta-cell compensatory adaptation to the increased insulin demand, causes the acute, long-term, and transgenerational health complications. The aim of the study was to assess if alterations in gene expression of microRNAs associated with diabetes/cardiovascular/cerebrovascular diseases are present in whole peripheral blood of children aged 3-11 years descending from GDM complicated pregnancies. A substantially altered microRNA expression profile was found in children descending from GDM complicated pregnancies. Almost all microRNAs with the exception of miR-92a-3p, miR-155-5p, and miR-210-3p were upregulated. The microRNA expression profile also differed between children after normal and GDM complicated pregnancies in relation to the presence of overweight/obesity, prehypertension/hypertension, and/or valve problems and heart defects. Always, screening based on the combination of microRNAs was superior over using individual microRNAs, since at 10.0% false positive rate it was able to identify a large proportion of children with an aberrant microRNA expression profile (88.14% regardless of clinical findings, 75.41% with normal clinical findings, and 96.49% with abnormal clinical findings). In addition, the higher incidence of valve problems and heart defects was found in children with a prior exposure to GDM. The extensive file of predicted targets of all microRNAs aberrantly expressed in children descending from GDM complicated pregnancies indicates that a large group of these genes is involved in ontologies of diabetes/cardiovascular/cerebrovascular diseases. In general, children with a prior exposure to GDM are at higher risk of later development of diabetes mellitus and cardiovascular/cerebrovascular diseases, and would benefit from dispensarisation as well as implementation of primary prevention strategies.
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Qi Y, Qian R, Jia L, Fei X, Zhang D, Zhang Y, Jiang S, Fu X. Overexpressed microRNA-494 represses RIPK1 to attenuate hippocampal neuron injury in epilepsy rats by inactivating the NF-κB signaling pathway. Cell Cycle 2020; 19:1298-1313. [PMID: 32308116 DOI: 10.1080/15384101.2020.1749472] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
OBJECTIVE The effects of microRNAs (miRNAs) have been identified in epilepsy (Ep) in recent years, our research was focused on the functions of miR-494 in Ep and its inner mechanisms. METHODS The Ep modeled rats induced by lithium chloride-pilocarpine were treated with agomir-miR-494 or RIPK1-siRNA. The pathology of rat hippocampal tissues was observed. Expression of miR-494, receptor-interacting protein kinase 1 (RIPK1) and nuclear factor-kappaB (NF-κB) p65 was assessed by RT-qPCR and Western blot analysis. The hippocampal neurons of epileptic rats were successfully modeled, which were transfected with miR-494 mimics or RIPK1-siRNA to determine neurons' proliferation ability and cell apoptosis. The target relation between miR-494 and RIPK1 was measured by bioinformatics website and dual luciferase gene reporter assay. RESULTS The expression of miR-494 was reduced, while the expression of RIPK1 and NF-κB p65 was amplified in hippocampus of Ep rats. Elevated miR-494 repressed the expression of RIPK1 to ameliorate the hippocampal neuron injury, accelerate neuronal proliferation, and restrain neuronal apoptosis via inactivating the NF-κB signaling pathway, causing a deceleration of Ep development. Furthermore, amplified RIPK1 was able to reverse the amelioration of neuronal injury in Ep rats which was contributed by upregulated miR-494. CONCLUSION We found in this study that elevated miR-494 repressed RIPK1, causing an inactivation of the NF-κB signaling pathway and acceleration of cell proliferation, and suppression of apoptosis of hippocampal neurons in Ep rats, thereby attenuating the neuron injury and Ep development. Our research may provide novel targets for the therapy of Ep.
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Affiliation(s)
- Yinbao Qi
- Department of Nuerosurgery, Shandong University , Jinan, Shandong Province, P. R. China.,Department of Neurosurgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, Anhui Province, P. R. China.,Department of Neurosurgery, Anhui Provincial Institute of Stereotactic Neurosurgery , Hefei, Anhui Province, P. R. China
| | - Ruobing Qian
- Department of Neurosurgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, Anhui Province, P. R. China.,Department of Neurosurgery, Anhui Provincial Institute of Stereotactic Neurosurgery , Hefei, Anhui Province, P. R. China
| | - Li Jia
- Department of Neurosurgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, Anhui Province, P. R. China.,Department of Neurosurgery, Anhui Provincial Institute of Stereotactic Neurosurgery , Hefei, Anhui Province, P. R. China
| | - Xiaorui Fei
- Department of Neurosurgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, Anhui Province, P. R. China.,Department of Neurosurgery, Anhui Provincial Institute of Stereotactic Neurosurgery , Hefei, Anhui Province, P. R. China
| | - Dong Zhang
- Department of Neurosurgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, Anhui Province, P. R. China.,Department of Neurosurgery, Anhui Provincial Institute of Stereotactic Neurosurgery , Hefei, Anhui Province, P. R. China
| | - Yiming Zhang
- Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University , Hefei, Anhui Province, P. R. China
| | - Sen Jiang
- Department of Neurosurgery, Anhui Provincial Hospital Affiliated to Anhui Medical University , Hefei, Anhui Province, P. R. China
| | - Xianming Fu
- Department of Nuerosurgery, Shandong University , Jinan, Shandong Province, P. R. China.,Department of Neurosurgery, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, Anhui Province, P. R. China.,Department of Neurosurgery, Anhui Provincial Institute of Stereotactic Neurosurgery , Hefei, Anhui Province, P. R. China
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Cubillos-Angulo JM, Vinhaes CL, Fukutani ER, Albuquerque VVS, Queiroz ATL, Andrade BB, Fukutani KF. In silico transcriptional analysis of mRNA and miRNA reveals unique biosignatures that characterizes different types of diabetes. PLoS One 2020; 15:e0239061. [PMID: 32956382 PMCID: PMC7505453 DOI: 10.1371/journal.pone.0239061] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Accepted: 08/28/2020] [Indexed: 12/19/2022] Open
Abstract
Diabetes (DM) has a significant impact on public health. We performed an in silico study of paired datasets of messenger RNA (mRNA) micro-RNA (miRNA) transcripts to delineate potential biosignatures that could distinguish prediabetes (pre-DM), type-1DM (T1DM) and type-2DM (T2DM). Two publicly available datasets containing expression values of mRNA and miRNA obtained from individuals diagnosed with pre-DM, T1DM or T2DM, and normoglycemic controls (NC), were analyzed using systems biology approaches to define combined signatures to distinguish different clinical groups. The mRNA profile of both pre-DM and T2DM was hallmarked by several differentially expressed genes (DEGs) compared to NC. Nevertheless, T1DM was characterized by an overall low number of DEGs. The miRNA signature profiles were composed of a substantially lower number of differentially expressed targets. Gene enrichment analysis revealed several inflammatory pathways in T2DM and fewer in pre-DM, but with shared findings such as Tuberculosis. The integration of mRNA and miRNA datasets improved the identification and discriminated the group composed by pre-DM and T2DM patients from that constituted by normoglycemic and T1DM individuals. The integrated transcriptomic analysis of mRNA and miRNA expression revealed a unique biosignature able to characterize different types of DM.
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Affiliation(s)
- Juan M. Cubillos-Angulo
- Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil
- Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil
- Curso de Medicina, Faculdade de Tecnologia e Ciências (FTC), Salvador, Brazil
| | - Caian L. Vinhaes
- Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil
- Curso de Medicina, Faculdade de Tecnologia e Ciências (FTC), Salvador, Brazil
- Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil
| | | | | | - Artur T. L. Queiroz
- Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil
- Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil
- * E-mail: (BBA); (ATLQ); (KFF)
| | - Bruno B. Andrade
- Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil
- Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil
- Curso de Medicina, Faculdade de Tecnologia e Ciências (FTC), Salvador, Brazil
- Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil
- Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador, Brazil
- Universidade Salvador (UNIFACS), Laureate Universities, Salvador, Brazil
- * E-mail: (BBA); (ATLQ); (KFF)
| | - Kiyoshi F. Fukutani
- Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil
- Curso de Medicina, Faculdade de Tecnologia e Ciências (FTC), Salvador, Brazil
- Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Salvador, Brazil
- * E-mail: (BBA); (ATLQ); (KFF)
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Zhou X, Xiang C, Zheng X. miR-132 serves as a diagnostic biomarker in gestational diabetes mellitus and its regulatory effect on trophoblast cell viability. Diagn Pathol 2019; 14:119. [PMID: 31653266 PMCID: PMC6814988 DOI: 10.1186/s13000-019-0899-9] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Accepted: 10/09/2019] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) leads to poor pregnancy outcomes. Strategies that improve trophoblast cell function are important methods for GDM treatment. This study aimed to investigate the expression and diagnostic potential of microRNA-132 (miR-132) in GDM patients, and further analyzed the effects of miR-132 on HTR-8/SVneo cell proliferation. METHODS Quantitative real-time PCR was applied to estimate the expression of miR-132. A receiver operating characteristics curve (ROC) analysis was performed to evaluate the diagnostic value of serum miR-132 in GDM patients. In vitro regulation of miR-132 in trophoblast cell HTR-8/SVneo was achieved by cell transfection, and the effects of miR-132 on cell proliferation were assessed using CCK-8 assay. RESULTS Expression of miR-132 was decreased in serum and placenta tissues in GDM patients compared with the healthy women. A negative correlation was found between the serum miR-132 levels and fasting blood glucose of the GDM patients. A ROC curve shown the serum miR-132 had considerable diagnostic accuracy with an area under the curve (AUC) of 0.898. High glucose (HG) treatment induced an inhibition in HTR-8/SVneo cell proliferation and the expression of miR-132. The overexpression of miR-132 in HTR-8/SVneo cells could markedly rescued the HG - induced suppressed cell proliferation. CONCLUSION All the data of this study revealed the reduced expression of miR-132 in serum and placenta tissues of GDM, and serum miR-132 serves a candidate biomarker in the diagnosis of GDM. miR-132 may act a protective role against GDM via enhancing the trophoblast cell proliferation.
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Affiliation(s)
- Xuegui Zhou
- Department of Obstetrics, Binzhou People's Hospital, No. 515, Huanghe 7 Road, Binzhou, Shandong, 256610, People's Republic of China.
| | - Cuiping Xiang
- Department of Obstetrics, Binzhou People's Hospital, No. 515, Huanghe 7 Road, Binzhou, Shandong, 256610, People's Republic of China
| | - Xiaoxia Zheng
- Department of Obstetrics, Binzhou Center Hospital, Binzhou, Shandong, 251700, People's Republic of China
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Zhao L, Sun LF, Zheng XL, Liu JF, Zheng R, Wang Y, Yang R, Zhang L, Yu L, Zhang H. [In vitro fertilization-embryo transfer affects focal adhension kinase signaling pathway in early placenta]. JOURNAL OF PEKING UNIVERSITY. HEALTH SCIENCES 2019; 51:151-158. [PMID: 30773560 DOI: 10.19723/j.issn.1671-167x.2019.01.026] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To study the effects of in vitro fertilization-embryo transfer (IVF-ET) technique on gene expression of focal adhension kinase (FAK) signaling pathway in early placental trophoblast cells, and to explore the effects of IVF-ET technology on the development and function of early placenta. METHODS We collected 7-8 weeks of gestation placenta tissue as a study group by ultrasound guided reduction of fetal from double embryo transfer under IVF-ET technology. In the control group, placenta tissues were obtained from the spontaneous abortion of natural pregnancy twin 7-8 weeks. Microarray hybridization analysis was performed on the placenta tissue of the two groups using the Affymetrix HG-U133 Plus 2.0 gene chip. Eight differentially expressed genes were identified by real-time quantitative polymerase chain reaction (qRT-PCR), and unsupervised clustering analysis and functional bioinformatics analysis were performed for the differentially expressed genes. RESULTS Twenty-eight cases of IVF-ET reduced fetal villi and 8 cases of spontaneous abortion villi were collected. A total of 8 placental villi were detected by the gene chip. Compared with the natural pregnancy control group, 32 differentially expressed genes in the placental FAK signaling pathway were expressed in IVF-ET. The differential expression was greater than or equal to 2 times, of which 12 genes were up-regulated and 20 were down-regulated. The qRT-PCR showed that the expression of the 8 genes in FAK signaling pathways of IVF-ET was significantly different from that in the placenta of natural pregnancy, which was consistent with the result of the gene chip detection. The FAK signal pathway gene localization showed that the FAK gene was mainly located in the upstream of the signal pathway in the placenta of IVF-ET. The placental trophoblast cells maintained the FAK signaling pathway function through gene expression compensation. CONCLUSION There are gene expression differences in the FAK signaling pathway between the IVF-ET derived early placenta and the natural pregnancy placenta. The differentially expressed genes are involved in many key functions of the FAK signaling pathway and affect the early development and function of the IVF-ET placenta, while the placental trophoblast cells change gene expression for interference to compensate for IVF-ET technology itself, maintain normal function of the FAK signaling pathway, and satisfy the need for placental and fetal development.
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Affiliation(s)
- L Zhao
- Department of Obstetrics and Gynecology, Beijing Jishuitan Hospital, Beijing 100035, China
| | - L F Sun
- Department of Obstetrics and Gynecology, Beijing Jishuitan Hospital, Beijing 100035, China
| | - X L Zheng
- Department of Obstetrics and Gynecology, Beijing Jishuitan Hospital, Beijing 100035, China
| | - J F Liu
- Department of Obstetrics and Gynecology, Beijing Jishuitan Hospital, Beijing 100035, China
| | - R Zheng
- Department of Obstetrics and Gynecology, Beijing Jishuitan Hospital, Beijing 100035, China
| | - Y Wang
- Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
| | - R Yang
- Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
| | - L Zhang
- Department of Obstetrics and Gynecology, Beijing Tsinghua Changgung Hospital, Beijing 102218, China
| | - L Yu
- Department of Obstetrics and Gynecology, Peking University First Hospital, Beijing 100034, China
| | - H Zhang
- Department of Obstetrics and Gynecology, Beijing Jishuitan Hospital, Beijing 100035, China
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Diabetes in Pregnancy and MicroRNAs: Promises and Limitations in Their Clinical Application. Noncoding RNA 2018; 4:ncrna4040032. [PMID: 30424584 PMCID: PMC6316501 DOI: 10.3390/ncrna4040032] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2018] [Revised: 10/29/2018] [Accepted: 11/05/2018] [Indexed: 12/12/2022] Open
Abstract
Maternal diabetes is associated with an increased risk of complications for the mother and her offspring. The latter have an increased risk of foetal macrosomia, hypoglycaemia, respiratory distress syndrome, preterm delivery, malformations and mortality but also of life-long development of obesity and diabetes. Epigenetics have been proposed as an explanation for this long-term risk, and microRNAs (miRNAs) may play a role, both in short- and long-term outcomes. Gestation is associated with increasing maternal insulin resistance, as well as β-cell expansion, to account for the increased insulin needs and studies performed in pregnant rats support a role of miRNAs in this expansion. Furthermore, several miRNAs are involved in pancreatic embryonic development. On the other hand, maternal diabetes is associated with changes in miRNA both in maternal and in foetal tissues. This review aims to summarise the existing knowledge on miRNAs in gestational and pre-gestational diabetes, both as diagnostic biomarkers and as mechanistic players, in the development of gestational diabetes itself and also of short- and long-term complications for the mother and her offspring.
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Molecular Biomarkers for Gestational Diabetes Mellitus. Int J Mol Sci 2018; 19:ijms19102926. [PMID: 30261627 PMCID: PMC6213110 DOI: 10.3390/ijms19102926] [Citation(s) in RCA: 64] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Revised: 09/21/2018] [Accepted: 09/22/2018] [Indexed: 12/20/2022] Open
Abstract
Gestational diabetes mellitus (GDM) is a growing public health problem worldwide. The condition is associated with perinatal complications and an increased risk for future metabolic disease in both mothers and their offspring. In recent years, molecular biomarkers received considerable interest as screening tools for GDM. The purpose of this review is to provide an overview of the current status of single-nucleotide polymorphisms (SNPs), DNA methylation, and microRNAs as biomarkers for GDM. PubMed, Scopus, and Web of Science were searched for articles published between January 1990 and August 2018. The search terms included “gestational diabetes mellitus”, “blood”, “single-nucleotide polymorphism (SNP)”, “DNA methylation”, and “microRNAs”, including corresponding synonyms and associated terms for each word. This review updates current knowledge of the candidacy of these molecular biomarkers for GDM with recommendations for future research avenues.
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