文献类型：期刊文献

英文题名：Long Noncoding RNA H19 Overexpression Inhibits High Glucose-Induced Oxidative Stress of Cardiomyocytes by Targeting MicroRNA-138-5p/MCU Axis: Implications for Diabetic Cardiomyopathy

作者：Liu, Xuelin[1,2];Zhang, Qian[1,2];Zhang, Yuemei[2];Dong, Jianting[1];Wang, Ruilin[2];Zhang, Qi[2,3];Chen, Yongqing[1]

第一作者：柳兴龙;刘小玲;刘晓丽;刘雪丽;Liu, Xuelin

通信作者：Chen, YQ[1]

机构：[1]Gansu Prov Cent Hosp, Dept Cardiol, Lanzhou 730070, Gansu, Peoples R China;[2]Gansu Univ Tradit Chinese Med, Clin Med Coll 1, Lanzhou 730000, Gansu, Peoples R China;[3]Xian Int Med Ctr Hosp, Dept Cardiol, Xian 710000, Shanxi, Peoples R China

第一机构：Gansu Prov Cent Hosp, Dept Cardiol, Lanzhou 730070, Gansu, Peoples R China

通信机构：[1]corresponding author), Gansu Prov Cent Hosp, Dept Cardiol, Lanzhou 730070, Gansu, Peoples R China.

年份：2025

外文期刊名：BIOCHEMICAL GENETICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001585447700001)】；

基金：Study on the Mechanism of Long Non-Coding RNA H19 Regulating MCU as a Competing Endogenous RNA in the Pathogenesis and Progression of Diabetic Cardiomyopathy, Natural Science Foundation of Gansu Province. Project Number: 23JRRA1377. Mechanistic Research on Mitochondrial Transcription Factor A Expression Alterations Mediating the Development of Diabetic Cardiomyopathy, Lanzhou Science and Technology Planning Project. Project Number: 2022-5-84.

语种：英文

外文关键词：Diabetic Cardiomyopathy; Long Noncoding RNA H19; MicroRNA-138-5p; Mitochondrial Calcium Uniporter; Oxidative Stress

摘要：This study investigates the regulatory effects of long non-coding RNA H19 on miR-138-5p and their collective impact on mitochondrial oxidative stress injury in high glucose-exposed cardiomyocytes, while elucidating the underlying molecular mechanisms. The findings aim to establish a theoretical foundation for understanding the pathogenesis of diabetic cardiomyopathy. The expression levels of lncRNA H19, miR-138-5p, and MCU were quantified using RT-qPCR. H9c2 cardiomyocytes were exposed to high glucose (HG, 33 mM) in vitro to establish a diabetic cardiomyopathy (DCM) model. Regulatory targeting relationships between lncRNA H19 and miR-138-5p, as well as between miR-138-5p and mitochondrial calcium uniporter(MCU), were confirmed through dual-luciferase reporter assays. Levels of reactive oxygen species (ROS), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content were quantified to evaluate intracellular oxidative stress in cardiomyocytes. MCU protein expression was analyzed by western blotting. In DCM, H19 and MCU were downregulated; miR-138-5p was upregulated. H19 overexpression increased SOD activity and reduced ROS and MDA levels in HG-treated H9c2 cardiomyocytes. Dual-luciferase assays validated miR-138-5p binding to H19 and MCU 3'UTRs. miR-138-5p overexpression suppressed MCU protein expression. Rescue experiments demonstrated miR-138-5p overexpression or MCU silencing reversed H19-mediated oxidative stress attenuation in HG-stimulated cells. Overexpression of H19 attenuates oxidative stress by modulating the miR-138-5p/MCU axis in DCM, highlighting its potential as a diagnostic biomarker and/or therapeutic target for this condition.