肌生成抑制素可抑制血管紧张素Ⅱ诱导的人诱导多能干细胞源性心肌细胞凋亡。
Myogenin suppresses apoptosis induced by angiotensin II in human induced pluripotent stem cell-derived cardiomyocytes.
机构信息
Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, 510100, China.
School of Medical Imaging, Tianjin Medical University, Tianjin, 300203, China.
出版信息
Biochem Biophys Res Commun. 2021 May 7;552:84-90. doi: 10.1016/j.bbrc.2021.03.031. Epub 2021 Mar 17.
BACKGROUND
Angiotensin II (Ang II), an important component of the renin-angiotensin system (RAS), plays a critical role in the pathogenesis of cardiovascular disorders. In addition, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been considered as a promising platform for studying personalized medicine for heart diseases. However, whether Ang II can induce the apoptosis of hiPSC-CMs is not known.
METHODS
In this study, we treated hiPSC-CMs with different concentrations of Ang II [0 nM (vehicle as a control), 1 nM, 10 nM, 100 nM, 1 μM, 10 μM, 100 μM, and 1 mM] for various time periods (24 h, 48 h, 6 days, and 10 days) and analyzed the viability and apoptosis of hiPSC-CMs.
RESULTS
We found that treatment with 1 mM Ang II for 10 days reduced the viability of hiPSC-CMs by 41% (p = 2.073E-08) and increased apoptosis by 2.74-fold, compared to the control group (p = 6.248E-12). MYOG, which encodes the muscle-specific transcription factor myogenin, was also identified as an apoptosis-suppressor gene in Ang II-treated hiPSC-CMs. Ectopic MYOG expression decreased the apoptosis and increased the viability of Ang II-treated hiPSC-CMs. Further analysis of the RNA sequencing (RNA-seq) data illustrated that myogenin ameliorated Ang II-induced apoptosis of hiPSC-CMs by downregulating the expression of proinflammatory genes.
CONCLUSION
Our findings suggest that Ang II induces the apoptosis of hiPSC-CMs and that myogenin attenuates Ang II-induced apoptosis.
背景
血管紧张素 II（Ang II）是肾素-血管紧张素系统（RAS）的重要组成部分，在心血管疾病的发病机制中起着关键作用。此外，人诱导多能干细胞衍生的心肌细胞（hiPSC-CMs）已被认为是研究心脏病个性化药物的有前途的平台。然而，Ang II 是否会诱导 hiPSC-CMs 凋亡尚不清楚。
方法
在这项研究中，我们用不同浓度的 Ang II [0 nM（作为对照的载体）、1 nM、10 nM、100 nM、1 μM、10 μM、100 μM 和 1 mM]处理 hiPSC-CMs 不同时间（24 h、48 h、6 天和 10 天），并分析 hiPSC-CMs 的活力和凋亡。
结果
我们发现，与对照组相比，用 1 mM Ang II 处理 10 天可使 hiPSC-CMs 的活力降低 41%（p=2.073E-08），凋亡增加 2.74 倍（p=6.248E-12）。编码肌肉特异性转录因子肌球蛋白的 MYOG 也被鉴定为 Ang II 处理的 hiPSC-CMs 中的凋亡抑制基因。异位 MYOG 表达可降低 Ang II 处理的 hiPSC-CMs 的凋亡并增加其活力。对 RNA 测序（RNA-seq）数据的进一步分析表明，肌球蛋白通过下调促炎基因的表达来改善 Ang II 诱导的 hiPSC-CMs 凋亡。
结论
我们的研究结果表明，Ang II 诱导 hiPSC-CMs 凋亡，肌球蛋白减弱 Ang II 诱导的凋亡。
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