Suppression of Sox4 protects against myocardial ischemic injury by reduction of cardiac apoptosis in mice
Suppression of Sox4 protects against myocardial ischemic injury by reduction of cardiac apoptosis in mice
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抑制 Sox4 通过减少小鼠心脏细胞凋亡来防止心肌缺血性损伤
DOI：
10.1002/jcp.29918
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发表时间：
2021-02-01
影响因子：
5.6
通讯作者：
Liang, Haihai
中科院分区：
文献类型：
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作者：
Zhang, Lijia;Lv, Lifang;Liang, Haihai
Sox 4参与胚胎发育和肿瘤细胞凋亡的调控。然而，Sox 4在心肌梗死（MI）中的作用和机制尚不清楚。因此，本研究旨在探讨Sox 4在MI心肌细胞凋亡过程中的作用及其分子机制。心肌梗死组和H2 O2处理的乳鼠心肌细胞Sox 4表达均明显增加。过表达Sox 4可促进H2 O2诱导的心肌细胞凋亡，而敲低Sox 4可减轻H2 O2诱导的心肌细胞凋亡。此外，通过AAV-9携带靶向Sox 4的短发夹RNA（AAV-9-sh-Sox 4）沉默Sox 4显著减少MI小鼠的心肌梗死面积，改善心功能障碍，并逆转细胞凋亡。从机制上讲，在Bim的启动子区域存在潜在的Sox 4结合位点，并且在有或没有H2 O2的培养心肌细胞中，Sox 4的强制表达显著促进Bim的表达，而敲低Sox 4抑制Bim的表达。进一步的研究表明，沉默Bim减弱了Sox 4诱导的心肌细胞凋亡，表明Sox 4通过调节Bim表达促进心肌细胞凋亡，这可以用作MI的潜在治疗靶点。
Sox4 participates in the progression of embryo development and regulation of apoptosis in tumors. However, the effect and mechanism of Sox4 in myocardial infarction (MI) remains unclear. Therefore, we aimed at examining the role and molecular mechanism of Sox4 in the process of cardiomyocytes apoptosis during MI. The expression of Sox4 were obviously increased both in MI mice and in neonatal mouse cardiomyocytes treated with H2O2. Overexpression of Sox4 promoted cardiomyocyte apoptosis with or without H2O2, whereas knocking down of Sox4 alleviated H2O2‐induced apoptosis in cardiomyocytes. Furthermore, silencing Sox4 by AAV‐9 carried short hairpin RNA targeting Sox4 (AAV‐9‐sh‐Sox4) markedly decreased cardiac infarct area, imprfoved cardiac dysfunction, and reversed apoptosis in MI mice. Mechanistically, there is a potential Sox4‐binding site in the promoter region of Bim, and forced expression of Sox4 significantly promoted Bim expression in cultured cardiomyocytes with or without H2O2, whereas knocking down of Sox4 inhibited the expression of Bim. Further studies showed that silencing Bim attenuated Sox4‐induced apoptosis in cardiomyocytes, indicating that Sox4 promoted cardiomyocytes apoptosis through regulation of Bim expression, which can be used as a potential therapeutic target for MI.