https://scholars.lib.ntu.edu.tw/handle/123456789/540561
標題: | MicroRNA-221/222 Mediates ADSC-Exosome-Induced Cardioprotection Against Ischemia/Reperfusion by Targeting PUMA and ETS-1 | 作者: | Lai, Tsai-Chun Lee, Tzu-Lin Chang, Yu-Chun Chen, Yu-Chen Lin, Shu-Rung SHU-WHA LIN Pu, Chi-Ming JAW-SHIUN TSAI YUH-LIEN CHEN |
關鍵字: | ADSC; adipose derived mesenchymal stem cell; apoptosis; exosome; hypertrophy; ischemia – reperfusion; miR-221 and 222 | 公開日期: | 2020 | 出版社: | FRONTIERS MEDIA SA | 卷: | 8 | 來源出版物: | Frontiers in cell and developmental biology | 摘要: | Cardiovascular disease is a major health problem in industrialized and developing countries and is the leading cause of death and disability. Myocardial ischemia/reperfusion (I/R) causes cardiomyocyte damage such as apoptosis and hypertrophy. The purpose of this study was to investigate the effects of exosomes from adipose-derived stem cells (ADSC-Exo) on hearts from I/R mice and to explore the underlying mechanisms. ADSC-Exo significantly decreased I/R-induced cardiomyocyte apoptosis and hypertrophy, as detected by TdT-mediated dUTP nick end-labeling (TUNEL) and wheat germ agglutinin (WGA) staining, respectively. In addition, the expression of apoptosis-related proteins p-p53 and PUMA and hypertrophy-related proteins ETS-1 and ANP were significantly reduced in the cardiomyocytes of ADSC-Exo-treated I/R mice compared to those of control mice. Both PUMA and ETS-1 are reported to be target genes for miR-221/222. I/R operation significantly reduced miR-221/222 expression, while ADSC-Exo treatment increased miR-221/222 expression, as detected by RT-qPCR. We also observed that cardiac I/R operation markedly increased cell apoptosis and hypertrophy in miR-221/222 knockout (KO) mice, while ADSC-Exo reduced the effects of I/R operation. Furthermore, ADSC-Exo protected H9c2 cardiomyocytes from H2O2-induced damage by reducing apoptosis and hypertrophy in vitro. H2O2 treatment significantly reduced miR-221/222 expression, while ADSC-Exo treatment reversed this effect in H9c2 cells. ADSC-Exo treatment decreased H2O2-induced PUMA and ETS-1 expression. Compared with control treatment, I/R treatment significantly reduced p-AKT and increased p-p65, while ADSC-Exo and miR-221/222 mimics attenuated these effects. The AKT activator SC79 and p65 inhibitor Bay 11-7082 reduced H2O2-induced cell apoptosis and hypertrophy. Based on these findings, ADSC-Exo prevents cardiac I/R injury through the miR-221/miR-222/PUMA/ETS-1 pathway. Therefore, ADSC-Exo is an effective inhibitor of I/R-induced heart injury. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/540561 | ISSN: | 2296-634X | DOI: | 10.3389/fcell.2020.569150 | SDG/關鍵字: | 3 (4 methylphenylsulfonyl) 2 propenenitrile; hydrogen peroxide; immunoglobulin enhancer binding protein; lactate dehydrogenase; microRNA 221; microRNA 222; protein kinase B; protein p53; PUMA protein; reactive oxygen metabolite; transcription factor Ets 1; wheat germ agglutinin; adipose derived stem cell; Akt signaling; animal cell; animal experiment; animal model; apoptosis; Article; cardiac muscle cell; cardiovascular disease; cell volume; controlled study; exosome; genetic transfection; H9c2(2-1) cell line; heart hypertrophy; heart protection; in vitro study; in vivo study; knockout mouse; male; mesenchymal stem cell; mouse; myocardial ischemia reperfusion injury; nonhuman; protein expression; protein function; protein phosphorylation; rat; real time reverse transcription polymerase chain reaction; RNA isolation; signal transduction; TUNEL assay; Western blotting |
顯示於: | 解剖學暨細胞生物學科所 |
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