title: lncRNA H19/miR-675 axis regulates cardiomyocyte apoptosis by targeting VDAC1 in diabetic cardiomyopathy.
abstract: We previously established a rat model of diabetic cardiomyopathy (DCM) and found that the expression of lncRNA H19 was significantly downregulated. The present study was designed to investigate the pathogenic role of H19 in the development of DCM. Overexpression of H19 in diabetic rats attenuated oxidative stress, inflammation and apoptosis, and consequently improved left ventricular function. High glucose was associated with reduced H19 expression and increased cardiomyocyte apoptosis. To explore the molecular mechanisms involved, we performed in vitro experiments using cultured neonatal rat cardiomyocytes. Our results showed that miR-675 expression was decreased in cardiomyocytes transfected with H19 siRNA. The 3'UTR of VDAC1 was cloned downstream of a luciferase reporter construct and cotransfected into HEK293 cells with miR-675 mimic. The results of luciferase assay indicated that VDAC1 might be a direct target of miR-675. The expression of VDAC1 was upregulated in cardiomyocytes transfected with miR-675 antagomir, which consequently promotes cellular apoptosis. Moreover, enforced expression of H19 was found to reduce VDAC1 expression and inhibit apoptosis in cardiomyocytes exposed to high glucose. In conclusion, our study demonstrates that H19/miR-675 axis is involved in the regulation of high glucose-induced apoptosis by targeting VDAC1, which may provide a novel therapeutic strategy for the treatment of DCM.
authors: Department of Cardiology, The First People's Hospital of Kunshan Affiliated to Jiangsu University, Kunshan, China.
authors: Xiangquan
authors: X
authors: Li
authors: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Hao
authors: H
authors: Wang
authors: Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors: Biao
authors: B
authors: Yao
authors: Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors: Weiting
authors: W
authors: Xu
authors: Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors: Jianchang
authors: J
authors: Chen
authors: Department of Cardiology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
authors: Xiang
authors: X
authors: Zhou
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications*; D058065:Diabetic Cardiomyopathies / Q000235:genetics* / Q000503:physiopathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D018384:Oxidative Stress; D062085:RNA, Long Noncoding / Q000235:genetics*; D051381:Rats; D013311:Streptozocin; D016276:Ventricular Function; D050995:Voltage-Dependent Anion Channel 1 / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C094335:H19 long non-coding RNA; C000626775:MIRN675 microRNA, rat; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C494764:Vdac1 protein, rat; D013311:Streptozocin; D050995:Voltage-Dependent Anion Channel 1