miR-21 Reduces Hydrogen Peroxide-Induced Apoptosis in c-kit(+) Cardiac Stem Cells In Vitro through PTEN/PI3K/Akt Signaling.
miR-21 Reduces Hydrogen Peroxide-Induced Apoptosis in c-kit(+) Cardiac Stem Cells In Vitro through PTEN/PI3K/Akt Signaling.
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miR-21 通过 PTEN/PI3K/Akt 信号传导减少体外 c-kit( ) 心脏干细胞中过氧化氢诱导的细胞凋亡
DOI：
10.1155/2016/5389181
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发表时间：
2016
影响因子：
--
通讯作者：
Shi B
中科院分区：
文献类型：
--
作者：
Deng W;Wang Y;Long X;Zhao R;Wang Z;Liu Z;Cao S;Shi B
心肌干细胞（CSCs）在梗死心肌中的低存活率阻碍了缺血性心肌病的细胞治疗。microRNA-21（miR-21）及其靶蛋白之一PTEN有助于许多细胞类型的存活和增殖，但它们在c-kit+ CSC中的促存活作用尚不清楚。因此，我们假设miR-21减少过氧化氢-（H2 O2-）诱导的c-kit+ CSC细胞凋亡，并估计了PTEN/PI 3 K/Akt信号传导对这种氧化环境的贡献。在c-kit+ CSC中，miR-21模拟物有效地减少了H2 O2诱导的细胞凋亡，如通过下调促凋亡蛋白caspase-3和Bax以及上调抗凋亡Bcl-2所证明的。此外，miR-21在c-kit+ CSC中的功能获得下调了PTEN的蛋白水平，尽管其mRNA水平变化不大;同时，miR-21过表达也增加了磷酸化Akt（p-Akt）。miR-21的抗凋亡作用与选择性PTEN抑制剂Phen（bpV）相当，而miR-21抑制剂或PI 3 K抑制剂LY 294002有效地减弱了miR-21的抗凋亡作用。综上所述，这些结果表明，miR-21在c-kit+ CSC中的抗H2 O2诱导的凋亡作用是由PTEN/PI 3 K/Akt信号传导贡献的。miR-21可能是促进c-kit+ CSC治疗缺血心肌的潜在分子。
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.
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DOI：
10.1074/jbc.m113.495531
发表时间：
2014-02-07
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Di Bernardini E;Campagnolo P;Margariti A;Zampetaki A;Karamariti E;Hu Y;Xu Q
通讯作者：
Xu Q
影响因子：
37.8
作者：
Bolli R;Tang XL;Sanganalmath SK;Rimoldi O;Mosna F;Abdel-Latif A;Jneid H;Rota M;Leri A;Kajstura J
通讯作者：
Kajstura J
影响因子：
9.5
作者：
Hong KU;Li QH;Guo Y;Patton NS;Moktar A;Bhatnagar A;Bolli R
通讯作者：
Bolli R
影响因子：
2.7
作者：
Cao S;Liu Y;Wang H;Mao X;Chen J;Liu J;Xia Z;Zhang L;Liu X;Yu T
通讯作者：
Yu T
影响因子：
--
作者：
Ciuffreda, Ludovica;Falcone, Italia;Milella, Michele
通讯作者：
Milella, Michele