Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8437138 | EBioMedicine | 2018 | 10 Pages |
Abstract
Therapeutic efficiency of cardiac progenitor cells (CPCs) transplantation is limited by its low survival and retention in infarcted myocardium. Autophagy plays a critical role in regulating cell death and apoptosis, but the role of microRNAs (miRNAs) in oxidative stress-induced autophagy of CPCs remains unclear. This study aimed to explore if miRNAs mediate autophagy of c-kit+ CPCs. We found that the silencing of miR-143 promoted the autophagy of c-kit+ CPCs in response to H2O2, and the protective effect of miR-143 inhibitor was abrogated by autophagy inhibitor 3-methyladenine (3-MA). Furthermore, autophagy-related gene 7 (Atg7) was identified as the target gene of miR-143 by dual luciferase reporter assays. In vivo, after transfection with miR-143 inhibitor, c-kit+ CPCs from green fluorescent protein transgenic mice were more observed in infarcted mouse hearts. Moreover, transplantation of c-kit+ CPCs with miR-143 inhibitor improved cardiac function after myocardial infarction. Take together, our study demonstrated that miR-143 mediates oxidative stress-induced autophagy to enhance the survival of c-kit+ CPCs by targeting Atg7, which will provide a complementary approach for improving CPC-based heart repair.
Keywords
autophagy-related gene 7LVIDssequestosome 1SQSTM1LVIDdmRFPATG73-MAIHDCPCSGFP3-methyladenineMyocardial infarctionAutophagyLeft ventricularischemic heart diseaseleft ventricular end diastolic volumeleft ventricular end-systolic volumemicroRNAsCardiac progenitor cellsHematoxylin and Eosingreen fluorescent proteinmonomeric red fluorescent proteinejection fractionfractional shortening
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Authors
Wenya Ma, Fengzhi Ding, Xiuxiu Wang, Qi Huang, Lai Zhang, Chongwei Bi, Bingjie Hua, Ye Yuan, Zhenbo Han, Mengyu Jin, Tianyi Liu, Ying Yu, Benzhi Cai, Zhimin Du,