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- (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.

Emerging Role of mTOR Signaling‐Related miRNAs in Cardiovascular Diseases

“…Thus, it appears that miR-21 plays an active role in disrupting the PTEN-AKT-mTOR pathway. Similar result was also observed in cardiac stem cells, where miR-21 reduced hydrogen peroxide- (H 2 O 2 -) induced apoptosis, as evidenced by the downregulation of caspase-3 and Bax and upregulation of the antiapoptotic Bcl-2 [ 205 ]. Overexpression of miR-21 suppressed the expression of PTEN, a direct target of miR-21, with simultaneous increased in the phosphorylation state of AKT.…”

PTEN enhances nasal epithelial cell resistance to TNFα‑induced inflammatory injury by limiting mitophagy via repression of the TLR4‑JNK‑Bnip3 pathway

“…Accordingly, these data identified PTEN as an endogenous defender against inflammation-mediated cellular damage in nasal epithelial cells. Previous studies have also illustrated the beneficial role of PTEN in acute kidney injury (28), diabetes (71), cardiomyopathy (72) and chronic fatty liver disease (73). Therefore, an approach to reverse PTEN activity could be considered as adjuvant therapy to enhance anti-inflammatory treatments in patients with chronic nasal and sinus inflammation, but this needs to be investigated further.…”

Long non‑coding RNA regulates hair follicle stem cell proliferation and differentiation through PI3K/AKT signal pathway

“…The results of the present study demonstrate that lncRNA5322 or miR-21 transfection lead to upregulation of the PI3K/AKT signaling pathway in HFTs. Deng et al (32) suggested that miR-21 reduced hydrogen peroxide-induced apoptosis in c-kit+ cardiac stem cells in vitro via PTEN/PI3K/AKT signaling. The findings of the present study indicate that agomir-21 blocks lncRNA5322-induced upregulation of the PI3K/AKT signaling pathway during HFT differentiation.…”