• acute kidney injury (AKI)
• chronic kidney disease (CKD)
• extracellular vesicles
• macrophages
• renal inflammatory disease

• Humans
• Extracellular Vesicles/metabolism
• Macrophages/metabolism
• Macrophages/immunology
• Macrophages/pathology
• Animals
• Inflammation/metabolism
• Inflammation/pathology
• Cell Communication
• Acute Kidney Injury/metabolism
• Acute Kidney Injury/pathology
• Biomarkers/metabolism
• Kidney Diseases/metabolism
• Kidney Diseases/pathology
• Kidney/pathology
• Kidney/metabolism
• Kidney/immunology
• Renal Insufficiency, Chronic/metabolism
• Renal Insufficiency, Chronic/pathology

• Cancer prevention
• Epithelial-mesenchymal transition
• Gastric cancer
• Immunology
• Inflammation
• Invasion and metastasis
• Tumor-associated macrophages

• Stomach Neoplasms/pathology
• Stomach Neoplasms/genetics
• Stomach Neoplasms/metabolism
• Epithelial-Mesenchymal Transition
• Humans
• Cathepsin L/metabolism
• Cathepsin L/genetics
• Animals
• Cell Line, Tumor
• Cell Movement
• Tumor Microenvironment
• Peritoneal Neoplasms/secondary
• Neoplasm Invasiveness
• Tumor-Associated Macrophages/metabolism
• Tumor-Associated Macrophages/immunology
• Mice
• Macrophages/metabolism
• Male
• Female
• Prognosis
• Mice, Nude

• Autophagy
• Mitochondria
• Quality control
• Renal fibrosis
• Renal tubular epithelial cells
• Telomere homeostasis

• Long non-coding RNA FENDRR
• MicroRNA-214
• Mitofusin 2

• Humans
• Myofibroblasts/metabolism
• Arecoline/adverse effects
• Arecoline/metabolism
• Reactive Oxygen Species/metabolism
• Oral Submucous Fibrosis/genetics
• Oral Submucous Fibrosis/metabolism
• Oral Submucous Fibrosis/pathology
• Mouth Mucosa/metabolism
• Fibroblasts
• MicroRNAs/genetics
• MicroRNAs/metabolism
• GTP Phosphohydrolases/genetics
• GTP Phosphohydrolases/metabolism
• GTP Phosphohydrolases/pharmacology
• Mitochondrial Proteins/genetics
• Mitochondrial Proteins/metabolism

• SGLT2 inhibitors
• chronic kidney disease
• inflammation
• nuclear factor kappa B
• renal fibrosis

• 1 CSRD VA

• Acute renal injury
• Cisplatin
• Kidney
• Macrophages
• Renal tubular epithelial cells

• Humans
• Cisplatin/toxicity
• Acute Kidney Injury/pathology
• Kidney/pathology
• Macrophages/pathology
• Epithelial Cells/pathology

• kidney disease
• macrophage polarization
• macrophages
• renal inflammation and fibrosis

• Animals
• Fibrosis
• Macrophages/metabolism
• Renal Insufficiency, Chronic/metabolism
• Nephritis/metabolism
• Inflammation/metabolism
• Disease Models, Animal

• (5R)-5-hydroxytriptolide
• Diabetic nephropathy
• Macrophage
• Renal tubular epithelial cell

• Mice
• Animals
• Diabetic Nephropathies/drug therapy
• Diabetic Nephropathies/metabolism
• Diabetes Mellitus, Experimental/metabolism
• Kidney/pathology
• Glucose/metabolism
• Macrophages
• Fibrosis

• Cisplatin-induced interstitial fibrosis
• Conditioned medium
• Ginkgo biloba extract
• HIF-1α/STAT3/IL-6 pathway
• Renal fibroblast activation
• Renal tubular epithelial cells

• TGIF2
• miR-424
• oral submucous fibrosis

• CSH-2022-D-004 Chung Shan Medical University Hospital

A growing number of studies have confirmed that immune cells play various key roles in the pathophysiology of acute kidney injury (AKI) development. After the resident immune cells and intrinsic renal cells are damaged by ischemia and hypoxia, drugs and toxins, more immune cells will be recruited to infiltrate through the release of chemokines, while the intrinsic cells promote macrophage polarity conversion, and the immune cells will promote various programmed deaths, phenotypic conversion and cycle arrest of the intrinsic cells, ultimately leading to renal impairment and fibrosis. In the complex and dynamic immune microenvironment of AKI, the bidirectional interaction between immune cells and intrinsic renal cells affects the prognosis of the kidney and the progression of fibrosis, and determines the ultimate fate of the kidney.

• National Natural Science Foundation of China

• epithelial-mesenchymal transition
• high blood pressure
• interleukin-17A
• macrophages

• Animals
• Blood Pressure
• Cadherins/metabolism
• Epithelial-Mesenchymal Transition
• Hypertension
• Interleukin-17/metabolism
• Kidney
• RNA, Messenger/metabolism
• Rats
• Rats, Inbred SHR
• Rats, Inbred WKY

• Epithelial–mesenchymal transition
• Fascin-1
• Macrophages inflammation
• NLRP3
• Renal fibrosis
• circACTR2
• miR-561

• Epithelial Cells/metabolism
• Epithelial-Mesenchymal Transition/genetics
• Female
• Fibrosis
• Humans
• Inflammasomes/genetics
• Inflammasomes/metabolism
• Inflammation/pathology
• Kidney Diseases/metabolism
• Macrophages/metabolism
• Male
• MicroRNAs/metabolism
• NLR Family, Pyrin Domain-Containing 3 Protein/genetics
• NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
• RNA, Circular/genetics

• 202103050649 General Project of Health Committee of Hunan Province
• 2018JJ3781 Natural Science Funds for Youth Fund of Hunan Province
• General Project of Health Committee of Hunan Province
• Natural Science Funds for Youth Fund of Hunan Province

Our previous study indicated that Ginkgo biloba leaf extract (EGb) could protect against cisplatin-induced acute kidney injury in rabbits. The present study aimed to determine the effects and potential molecular mechanisms of EGb on chronic renal interstitial fibrosis induced by cisplatin using in vivo and in vitro models.

Rats received a single dose of cisplatin on Day 1, and a subset of rats was intraperitoneally injected with EGb daily between Days 22–40. In vitro, HK-2 cells were treated with cisplatin, and a subset of cells was cultivated with EGb or SIS3 (Smad3 inhibitor) for 48 h. Renal function of rats was assessed by detecting the levels of serum creatinine (Scr), blood urea nitrogen (BUN) and urinary N-acetyl-β-D-glucosaminidase (NAG). Hematoxylin and eosin staining and Masson’s trichrome staining were used to evaluate the damage and fibrosis of renal tissue. Western blotting, immunohistochemistry and immunofluorescence were used to detect the protein levels of fibrosis-associated proteins and signaling pathway-related proteins. RT–qPCR analysis was used to examine the mRNA levels of related indicators.

EGb significantly decreased the increased levels of Scr, BUN and urinary NAG and attenuated renal damage and the relative area of renal interstitial fibrosis induced by cisplatin. Additionally, EGb decreased the protein levels of α-SMA, Col I, TGF-β1, smad2/3, phosphorylated (p)-smad2/3, p38 MAPK, and p-p38 MAPK; the ratio of p-p38 MAPK/p38 MAPK; and the mRNA level of p38 MAPK in renal tissues induced by cisplatin. In agreement with in vivo studies, EGb significantly reduced the increased protein levels of these indicators. Additionally, EGb significantly reduced the increased protein levels of vimentin, TIMP-1, and CTGF, as well as the mRNA levels of α-SMA, vimentin, and TGF-β1, while it significantly increased the reduced E-cadherin protein level and the MMP-1/TIMP-1 ratio in HK-2 cells induced by cisplatin. It’s worth noting that the effects of SIS3 in changing the above indicators were similar to those of EGb.

Our study demonstrated that EGb improved cisplatin-induced chronic renal interstitial fibrosis, and its mechanisms were associated with inhibiting the epithelial-mesenchymal transition of renal tubular epithelial cells via the Smad3/TGF-β1 and Smad3/p38 MAPK pathways.

The online version contains supplementary material available at 10.1186/s13020-022-00574-y.

• Cisplatin
• Epithelial-mesenchymal transition
• Ginkgo biloba leaf extract
• Renal interstitial fibrosis
• Smad3/TGF- β1
• Smad3/p38 MAPK pathway

• Creb5
• Gas5
• ceRNA network
• lncRNA
• renal fibrosis

• Animals
• Cell Line
• Cyclic AMP Response Element-Binding Protein A/genetics
• Fibronectins/metabolism
• Fibrosis
• Kidney/pathology
• Male
• Mice, Inbred C57BL
• RNA, Long Noncoding/genetics
• Up-Regulation
• Mice

Ginaton injection (Ginkgo biloba extract; GBE) has been reported to protect against cisplatin-induced acute renal failure in rats. In the present study, the effects and molecular mechanisms of GBE on cisplatin-induced renal interstitial fibrosis were evaluated using a rat model. The rats were intraperitoneally injected with cisplatin once on the first day and a subset of rats were treated with GBE or SB203580 (SB; a specific p38 MAPK inhibitor) daily from days 22 to 40. The levels of N-acetyl-β-D-Glucosaminidase (NAG) in the urine, and of urea nitrogen (BUN) and creatinine (Scr) in the blood were assessed. The damage and fibrosis of renal tissues were evaluated using hematoxylin and eosin staining, as well as Masson's trichrome staining, respectively. Apoptosis in renal tissues was detected using a TUNEL assay. The protein expression levels of α-smooth muscle actin (SMA), collagen 1 (Col I), Bax, Bcl-2, caspase-3/cleaved caspase-3, hypoxia-inducible factor-1α (HIF-1α), TGF-β1 and p38MAPK, as well as the mRNA levels of p38MAPK in renal tissues were investigated. The results showed that GBE markedly reduced the levels of urinary NAG, Scr and BUN, and renal expression of α-SMA and Col I levels were also reduced. Furthermore, GBE significantly reduced renal tissue injury and the relative area of renal interstitial fibrosis induced by cisplatin. GBE effectively reduced the apoptotic rate of renal tissues, the protein expression levels of Bax, cleaved caspase-3, phospho-p38MAPK, TGF-β1 and HIF-1α, as well as the mRNA expression levels of p38MAPK in renal tissues induced by cisplatin, whereas GBE significantly increased Bcl-2 protein expression. SB exhibited similar effects to GBE, although it was not as effective. In summary, the present study is the first to show that GBE significantly alleviated renal interstitial fibrosis following cisplatin-induced acute renal injury. The mechanisms by which GBE exhibited its effects were associated with the inhibition of apoptosis via downregulation of the p38MAPK/TGF-β1 and p38MAPK/HIF-1α signaling pathways.

• apoptosis
• cisplatin-induced renal interstitial fibrosis
• ginaton injection
• hypoxia-inducible factor-1α
• p38MAPK

The aim of this study was to investigate the effect of the tumor-associated macrophage-m2-cancer cell complex (TAM-M2-CC) on the heterostructural modification of lung adenocarcinoma.

The expression of CD163+/CD68+ in macrophages in the microenvironment of 161 cases of lung adenocarcinoma was identified by dual immunohistochemistry, and the association between a TAM-M2-CC and its growth, as well as the histological changes in lung adenocarcinoma cells, was assessed.

The morphological change of lung adenocarcinoma was related to the number of m2 phenotypes of the macrophages in the microenvironment of lung adenocarcinoma. TAM-M2-CCs were involved in the process of cancer cell recognition, association, and reconstruction.

The microenvironment of lung adenocarcinoma can affect the phenotypic distinction of macrophages, and the polarization recruitment, zombification, and formation of a TAM-M2-CC, which can also affect the local differentiation of lung adenocarcinoma to a certain extent. The applicable pathogenesis needs to be verified and studied further.

• TAM-M2-CC
• heterostructural modification
• local differentiation
• microenvironment of lung adenocarcinoma
• phenotypic differentiation
• tumor-related macrophage-M2-cancer cell complex

• Anti viral activity
• CD8+T cells
• COVID 19 infection
• M1/ M2 macrophages
• adoptive immunotheraoy

• EGFR
• HuR
• MMP
• TGFβ
• cancer
• epithelial-to-mesenchymal transition, EMT
• fibrosis
• inflammation

• COPD
• Epithelial–mesenchymal transition
• Exosome
• Extracellular vesicle
• M2 macrophages
• Small airway remodeling
• miR-21

Henoch-Schönlein purpura (HSP) is the most common systemic vasculitis in children, and renal involvement (HSP nephritis, HSPN) is a severe manifestation. HSPN is histologically classified by the International Study of Kidney Disease in Children (ISKDC) based on mesangial hypercellularity and the extent of glomerular crescents. Macrophages, categorized as M1 or M2, frequently infiltrate in various glomerular and tubulointerstitial diseases and infiltration of specific subtypes is associated with disease progression. Therefore, to identify whether infiltration of M1 or M2 macrophages has clinical significance, we quantified the subtypes of macrophages in 49 HSPN specimens and correlated the counts with histologic features and clinical parameters. Higher tubulointerstitial M2 counts were associated with chronic renal failure (CRF), ISKDC classes III-IV, and crescents (P<0.001, 0.002, 0.001). Glomerular M2 counts were significantly related to ISKDC classes III-IV and crescents (area under curve, AUC 0.804, 0.833). Tubulointerstitial M2 counts were associated with CRF, ISKDC classes III-IV, and crescents (AUC 0.872, 0.778, 0.830). Tubulointerstitial M2 counts also revealed higher AUC than tubulointerstitial M1 counts for CRF (P=0.036) and ISKDC classes III-IV (P=0.047). Glomerular M2 counts revealed higher AUC than glomerular M1 counts for ISKDC classes III–IV (P=0.024). Tubulointerstitial M2 counts were the most powerful parameter for CRF (AUC 0.872) and revealed even higher AUC than ISKDC classification (AUC 0.716) with borderline significance (P=0.086) for CRF. In summary, tubulointerstitial M2 counts were a superior parameter to tubulointerstitial M1 counts and even to ISKDC classification indicating the presence of CRF.

• deep vein thrombosis
• national health insurance program
• older people
• pulmonary embolism
• taiwan
• tamoxifen

• Aged
• Antineoplastic Agents, Hormonal/adverse effects
• Antineoplastic Agents, Hormonal/therapeutic use
• Breast Neoplasms/drug therapy
• Breast Neoplasms/epidemiology
• Case-Control Studies
• Female
• Humans
• Pulmonary Embolism/epidemiology
• Pulmonary Embolism/etiology
• Retrospective Studies
• Taiwan/epidemiology
• Tamoxifen/adverse effects
• Tamoxifen/therapeutic use
• Venous Thrombosis/epidemiology
• Venous Thrombosis/etiology

• epidemiology
• gastrectomy
• pulmonary tuberculosis

• Adult
• Aged
• Cohort Studies
• Databases, Factual
• Female
• Gastrectomy/adverse effects
• Humans
• Incidence
• Male
• Middle Aged
• Proportional Hazards Models
• Risk Assessment
• Risk Factors
• Taiwan/epidemiology
• Tuberculosis, Pulmonary/epidemiology
• Tuberculosis, Pulmonary/etiology

• cancer stem cells
• cisplatin
• coculture techniques
• drug resistance
• epithelial-mesenchymal transition
• macrophages
• ovarian neoplasms

Chondrosarcoma is a malignant tumor of mesenchymal origin predominantly composed of cartilage-producing cells. This type of bone cancer is extremely resistant to radiotherapy and chemotherapy. Surgical resection is the primary treatment, but is often difficult and not always practical for metastatic disease, so more effective treatments are needed. In particular, it would be helpful to identify molecular markers as targets for therapeutic intervention. Endothelin-1 (ET-1), a potent vasoconstrictor, has been shown to enhance chondrosarcoma angiogenesis and metastasis. We report that ET-1 promotes epithelial–mesenchymal transition (EMT) in human chondrosarcoma cells. EMT is a key pathological event in cancer progression, during which epithelial cells lose their junctions and apical-basal polarity and adopt an invasive phenotype. Our study verifies that ET-1 induces the EMT phenotype in chondrosarcoma cells via the AMP-activated protein kinase (AMPK) pathway. In addition, we show that ET-1 increases EMT by repressing miR-300, which plays an important role in EMT-enhanced tumor metastasis. We also show that miR-300 directly targets Twist, which in turn results in a negative regulation of EMT. We found a highly positive correlation between ET-1 and Twist expression levels as well as tumor stage in chondrosarcoma patient specimens. Therefore, ET-1 may represent a potential novel molecular therapeutic target in chondrosarcoma metastasis.

• AMPK
• Twist
• epithelial to mesenchymal transition
• miR-300
• endothelin-1

Objectives: The purpose of the study was to assess the relationship between selective serotonin reuptake inhibitors use and hepatocellular carcinoma in Taiwan.

Methods: Using the database of the Taiwan National Health Insurance Program, we conducted a case-control study to identify 4901 subjects aged 20 years and more with newly diagnosed hepatocellular carcinoma in 2000–2013 as the cases. We randomly selected 19604 subjects aged 20 years and more without hepatocellular carcinoma as the controls. Both cases and controls were matched with sex and age. Ever use of selective serotonin reuptake inhibitors was defined as a subject who had at least a prescription for selective serotonin reuptake inhibitors before index date. Never use was defined as a subject who never had a prescription for selective serotonin reuptake inhibitors before index date. The odds ratio (OR) and 95% confidence interval (CI) for hepatocellular carcinoma associated with selective serotonin reuptake inhibitors use was estimated by the multivariable logistic regression model.

Results: Among subjects with any one of the comorbid conditions associated with hepatocellular carcinoma, the adjusted OR of hepatocellular carcinoma was 0.89 (95% CI 0.75, 1.06) for subjects with ever use of selective serotonin reuptake inhibitors, comparing with never use.

Conclusion: The findings indicate that among subjects with any one of the comorbid conditions associated with hepatocellular carcinoma, no significant association can be detected between selective serotonin reuptake inhibitors use and hepatocellular carcinoma.

• National Health Insurance Program
• Taiwan
• case-control study
• hepatocellular carcinoma
• selective serotonin reuptake inhibitors

• DPP-4 inhibitors
• National Health Insurance Program
• Taiwan
• diabetes mellitus
• ischemic cerebrovascular disease

• Older
• Parkinson’s disease
• Taiwan National Health Insurance Program
• Tamoxifen

• Alcohol-related disease
• biliary stone
• diabetes mellitus
• predialysis chronic kidney disease
• pyogenic liver abscess

• head and neck cancer
• incidence
• pulmonary tuberculosis
• taiwan national health insurance program

• Adult
• Age Factors
• Databases, Factual
• Female
• Head and Neck Neoplasms/microbiology
• Humans
• Incidence
• Male
• Middle Aged
• Proportional Hazards Models
• Retrospective Studies
• Risk Factors
• Sex Factors
• Taiwan/epidemiology
• Tuberculosis, Pulmonary/epidemiology
• Tuberculosis, Pulmonary/etiology

Aim: Little is known regarding the relationship between use of oral corticosteroids and hip fracture in the elderly in Taiwan. The aim of the study was to examine this issue.

Methods: A retrospective population-based case-control study using the database of the Taiwan National Health Insurance Program (2000–2013) was conducted. We identified 4538 individuals aged ≥ 65 years with newly diagnosed hip fracture as the cases. We randomly selected 4538 individuals without hip fracture as the control subjects. The cases and the control subjects were matched with sex, age, comorbidities, and the year of index date. Individuals who never had a prescription for oral corticosteroids were defined as never use. Individuals who ever had at least one prescription for oral corticosteroids were defined as ever use. The odds ratio (OR) and 95% confidence interval (CI) of hip fracture associated with oral corticosteroids use was estimated by a multivariable unconditional logistic regression analysis.

Results: After adjustments for potential confounding factors, the multivariable logistic regression model showed that the adjusted OR of hip fracture was 1.17 for individuals with ever use of oral corticosteroids (95%CI 1.08, 1.28), compared to those with never use of oral corticosteroids. An sub-analysis showed that for every 1-mg increase in cumulative dose of oral corticosteroids, the adjusted OR of hip fracture was 1.01 (95% CI 1.01, 1.02). The adjusted ORs were 1.31 (95% CI 1.17, 1.47) for cumulative exposure to oral corticosteroids ≥ 3 months and 1.09 (95% CI 0.98, 1.20) for cumulative exposure < 3 months.

Conclusion: We conclude that oral corticosteroids use is associated with a trivial but statistically significant increase in risk of hip fracture in Taiwan. Additionally, the results suggest that there are dose-response and duration-response effects of oral corticosteroids on the risk of hip fracture. The results confirm our understanding of oral corticosteroid-associated hip fracture in the elderly.

• elderly
• hip fracture
• oral corticosteroids

• Alzheimer’s disease
• Taiwan National Health Insurance Program
• breast cancer
• tamoxifen
• woman

• diabetes mellitus
• pleural empyema
• taiwan national health insurance program

• Adult
• Aged
• Aged, 80 and over
• Diabetes Mellitus/epidemiology
• Empyema, Pleural/epidemiology
• Female
• Humans
• Incidence
• Male
• Middle Aged
• Proportional Hazards Models
• Pulmonary Disease, Chronic Obstructive/epidemiology
• Retrospective Studies
• Risk Factors
• Sex Factors
• Taiwan/epidemiology
• Young Adult

• Acute pancreatitis
• Selective serotonin reuptake inhibitors

Background and Objectives: Although the relationship between the use of proton pump inhibitors (PPIs) and pulmonary tuberculosis (TB) in Taiwan published in 2014. Due to just only one article and not enough comprehensively, we explore this issue.

Methods: We conducted a population-based case-control study to identify 9,422 subjects aged 20 years or older with newly diagnosed pulmonary TB in 2000–2013 as test cases. We then randomly selected 9,422 subjects aged 20 years or older without pulmonary TB as controls. Both cases and controls were matched in terms of sex, age, and comorbidities. Use of PPIs were defined as subjects who had had at least one prescription for these medications before the index date. No use was defined as subjects who had never had a prescription for PPIs before the index date. The odds ratio (OR) and 95% confidence interval (CI) for pulmonary TB associated with PPI use was estimated using the logistic regression model.

Results: The OR of pulmonary TB was 1.31 for subjects who had used PPIs (95% CI 1.22, 1.41) compared with those with no use of the medications. Sub-analysis revealed the OR of pulmonary TB in subjects using PPI per increasing microgram was 1.25 (95% CI 1.19, 1.30).

Conclusions: PPI use is associated with a 1.3-fold increase in odds of developing pulmonary TB in Taiwan. There is a dose-related response between PPI use and pulmonary TB.

• Taiwan National Health Insurance Program
• proton pump inhibitors
• pulmonary tuberculosis

• EMT
• ER stress
• chemotherapeutics
• invasion
• migration

• Adenocarcinoma/drug therapy
• Adenocarcinoma/metabolism
• Adenocarcinoma/pathology
• Animals
• Antineoplastic Agents/pharmacology
• Apoptosis/drug effects
• Biomarkers, Tumor/metabolism
• Cell Movement/drug effects
• Cell Proliferation/drug effects
• Endoplasmic Reticulum/drug effects
• Endoplasmic Reticulum Stress/drug effects
• Epithelial-Mesenchymal Transition/drug effects
• Humans
• Lung Neoplasms/drug therapy
• Lung Neoplasms/metabolism
• Lung Neoplasms/pathology
• Male
• Mice
• Mice, Inbred C57BL
• Neoplasm Metastasis
• Neoplasm Staging
• Prognosis
• Tumor Cells, Cultured
• Unfolded Protein Response/drug effects
• Xenograft Model Antitumor Assays

• P20 GM103482 NIGMS NIH HHS
• R01 CA193220 NCI NIH HHS
• R01 DK093462 NIDDK NIH HHS

• Asiatic acid (AA)
• Bleomycin (BLM)
• Fibrosis
• Inflammation
• Pulmonary fibrosis

Pigment epithelium-derived factor (PEDF) is a multifunctional protein that exhibits anti-angiogenic, antitumor, anti-inflammatory, antioxidative, anti-atherogenic, and cardioprotective properties. While it was recently shown that PEDF expression is inhibited under low oxygen conditions, the functional role of PEDF in response to hypoxia/reoxygenation (H/R) remains unclear. The goal of this study was to therefore investigate the influence of PEDF on myocardial H/R injury. For these analyses, PEDF-specific small interfering RNA-expressing and PEDF-expressing lentivirus (PEDF-LV) vectors were utilized to knockdown or stably overexpress PEDF, respectively, within human cardiomyocytes (HCM) in vitro. We noted that reactive oxygen species (ROS) play important roles in the induction of cell death pathways, including apoptosis and autophagy in ischemic hearts. Our findings demonstrate that overexpression of PEDF resulted in a significant reduction in ROS production and attenuation of mitochondrial membrane potential depletion under H/R conditions. Furthermore, PEDF inhibited the activation of a two-step apoptotic pathway in which caspase-dependent (caspase-9 and caspase-3) and caspase-independent (apoptosis inducing factor and endonuclease G), which in turn cleaves several crucial substrates including the DNA repair enzyme poly (ADP-ribose) polymerase. Meanwhile, overexpression of PEDF also promoted autophagy, a process that is typically activated in response to H/R. Therefore, these findings suggest that PEDF plays a critical role in preventing H/R injury by modulating anti-oxidant and anti-apoptotic factors and promoting autophagy.

• Apoptosis
• Autophagy
• Caspases/metabolism
• Cell Hypoxia
• Cell Survival
• Cells, Cultured
• Eye Proteins/genetics
• Eye Proteins/metabolism
• Gene Expression Regulation
• Gene Knockdown Techniques
• Humans
• Membrane Potential, Mitochondrial
• Mitochondria/physiology
• Models, Biological
• Myocytes, Cardiac/cytology
• Myocytes, Cardiac/metabolism
• Nerve Growth Factors/genetics
• Nerve Growth Factors/metabolism
• Reactive Oxygen Species/metabolism
• Serpins/genetics
• Serpins/metabolism

• Kaohsiung Medical University
• Kaohsiung Municipal Ta-Tung Hospital
• China Medical University
• Taiwan Ministry of Science and Technology
• Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence