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整合素 β3 抑制心肌细胞缺氧诱导的细胞凋亡。

Integrin β3 inhibits hypoxia-induced apoptosis in cardiomyocytes.

机构信息

Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2018 Jul 1;50(7):658-665. doi: 10.1093/abbs/gmy056.

Abstract

Hypoxia-induced apoptosis plays an important role in cardiovascular diseases. Integrin β3 is one of the main integrin heterodimer receptors on the surface of cardiac myocytes. However, despite the important role that integrin β3 plays in the cardiovascular disease, its exact role in the hypoxia response remains unclear. Hence, in the present investigation we aimed to study the role of integrin β3 in hypoxia-induced apoptosis in H9C2 cells and primary rat myocardial cells. MTT assay, flow cytometry and TUNEL assay results showed that hypoxia inhibited cardiomyocyte proliferation and induced cardiomyocyte apoptosis. The expression levels of integrin β3 and HIF1α were upregulated in hypoxia-induced cardiomyocytes as revealed by real-time PCR and western blot analysis. Furthermore, knockdown of integrin β3 expression by siRNA increased hypoxia-induced cardiomyocyte apoptosis. In addition, integrin β3 overexpression weakened hypoxia-induced cardiomyocyte apoptosis. The protein expressions of integrin β3 and HIF1α were upregulated in acute myocardial infarction rat cardiac tissues compared with the control rat cardiac tissues. Our data suggest that integrin β3 plays a protective role in cardiomyocytes during hypoxia-induced apoptosis.

摘要

缺氧诱导的细胞凋亡在心血管疾病中发挥着重要作用。整合素β3 是心肌细胞表面主要的整合素异二聚体受体之一。然而,尽管整合素β3 在心血管疾病中发挥着重要作用,但它在缺氧反应中的确切作用仍不清楚。因此,在本研究中,我们旨在研究整合素β3 在 H9C2 细胞和原代大鼠心肌细胞缺氧诱导的细胞凋亡中的作用。MTT 检测、流式细胞术和 TUNEL 检测结果表明,缺氧抑制心肌细胞增殖并诱导心肌细胞凋亡。实时 PCR 和 Western blot 分析显示,缺氧诱导的心肌细胞中整合素β3 和 HIF1α 的表达水平上调。此外,siRNA 下调整合素β3 的表达可增加缺氧诱导的心肌细胞凋亡。此外,整合素β3 的过表达可减弱缺氧诱导的心肌细胞凋亡。与对照组大鼠心脏组织相比,急性心肌梗死大鼠心脏组织中整合素β3 和 HIF1α 的蛋白表达上调。我们的数据表明,整合素β3 在缺氧诱导的细胞凋亡过程中对心肌细胞发挥保护作用。

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