By Targeting Atg7 MicroRNA-143 Mediates Oxidative Stress-Induced Autophagy of c-Kit⁺ Mouse Cardiac Progenitor Cells.

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.

SUBMITTER: Ma W 

PROVIDER: S-EPMC6021267 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature