miR-21 Reduces Hydrogen Peroxide-Induced Apoptosis in c-kit+Cardiac Stem Cells In Vitro through PTEN/PI3K/Akt Signaling.
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- (H2O2-) induced apoptosis in c-kit+CSC and estimated the contribution of PTEN/PI3K/Akt signaling to this oxidative circumstance. miR-21 mimics efficiently reduced H2O2-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-H2O2-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.
Department of Cardiology, Affiliated Hospital of Zunyi Medical College, Zunyi 563000, China.
Wenwen
0000-0002-4247-5229
W
Deng
Department of Cardiology, Affiliated Hospital of Zunyi Medical College, Zunyi 563000, China.
Yan
Y
Wang
Department of Cardiology, Affiliated Hospital of Zunyi Medical College, Zunyi 563000, China.
Xianping
X
Long
Department of Cardiology, Affiliated Hospital of Zunyi Medical College, Zunyi 563000, China.
Ranzun
R
Zhao
Department of Cardiology, Affiliated Hospital of Zunyi Medical College, Zunyi 563000, China.
Zhenglong
Z
Wang
Department of Cardiology, Affiliated Hospital of Zunyi Medical College, Zunyi 563000, China.
Zhijiang
Z
Liu
Department of Anesthesiology, Zunyi Medical College, Zunyi 563000, China; Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical College, Zunyi 563000, China.
Song
0000-0003-4619-9441
S
Cao
Department of Cardiology, Affiliated Hospital of Zunyi Medical College, Zunyi 563000, China.
Bei
0000-0001-5316-2351
B
Shi
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002469:Cell Separation; D015536:Down-Regulation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology*; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013234:Stem Cells / Q000378:metabolism*
D035683:MicroRNAs; C546082:mirn21 microRNA, rat; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D019009:Proto-Oncogene Proteins c-kit; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase