miR‐21 Reduces Hydrogen Peroxide‐Induced Apoptosis in c‐kit⁺ Cardiac Stem Cells In Vitro through PTEN/PI3K/Akt Signaling

Abstract

The low survival rate of cardiac stem cells (CSCs) in the infarcted myocardium hampers cell therapy for ischemic cardiomyopathy. MicroRNA‐21 (miR‐21) and one of its target proteins, PTEN, contribute to the survival and proliferation of many cell types, but their prosurvival effects in c‐kit + CSC remain unclear. Thus, we hypothesized that miR‐21 reduces hydrogen peroxide‐ (H 2 O 2 ‐) induced apoptosis in c‐kit + CSC and estimated the contribution of PTEN/PI3K/Akt signaling to this oxidative circumstance. miR‐21 mimics efficiently reduced H 2 O 2 ‐induced apoptosis in c‐kit + CSC, as evidenced by the downregulation of the proapoptosis proteins caspase‐3 and Bax and upregulation of the antiapoptotic Bcl‐2. In addition, the gain of function of miR‐21 in c‐kit + CSC downregulated the protein level of PTEN although its mRNA level changed slightly; in the meantime, miR‐21 overexpression also increased phospho‐Akt (p‐Akt). The antiapoptotic effects of miR‐21 were comparable with Phen (bpV), the selective inhibitor of PTEN, while miR‐21 inhibitor or PI3K’s inhibitor LY294002 efficiently attenuated the antiapoptotic effect of miR‐21. Taken together, these results indicate that the anti‐H 2 O 2 ‐induced apoptosis effect of miR‐21 in c‐kit + CSC is contributed by PTEN/PI3K/Akt signaling. miR‐21 could be a potential molecule to facilitate the c‐kit + CSC therapy in ischemic myocardium.