Suppression of Sox4 protects against myocardial ischemic injury by reduction of cardiac apoptosis in mice.,Journal of Cellular Physiology

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Suppression of Sox4 protects against myocardial ischemic injury by reduction of cardiac apoptosis in mice.
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-07-13 , DOI: 10.1002/jcp.29918
Lijia Zhang ₁ , Lifang Lv _{1,

2} , Nan Zheng ₁ , Ruotong Li ₁ , Rui Yang ₁ , Tianyu Li _{1,

3} , Yingnan Li ₁ , Yingqi Liu ₁ , Hongwei Luo ₁ , Xuelian Li ₁ , Yuhong Zhou ₁ , Hongli Shan _{1,

3} , Bing Bai _{4,

5} , Haihai Liang _{1,

3}

Affiliation

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.

中文翻译：

抑制 Sox4 通过减少小鼠心脏细胞凋亡来防止心肌缺血损伤。

Sox4 参与胚胎发育的进程和肿瘤细胞凋亡的调节。然而，Sox4 在心肌梗死 (MI) 中的作用和机制仍不清楚。因此，我们旨在研究Sox4在MI期间心肌细胞凋亡过程中的作用和分子机制。在MI小鼠和用H ₂ O ₂处理的新生小鼠心肌细胞中Sox4的表达均明显增加。Sox4的过表达在有或没有H ₂ O _{2 的}情况下促进心肌细胞凋亡，而Sox4的敲低减轻了H ₂ O ₂诱导心肌细胞凋亡。此外，通过携带靶向 Sox4 的短发夹 RNA（AAV-9-sh-Sox4）的 AAV-9 沉默 Sox4 显着减少了心肌梗塞面积，改善了心脏功能障碍，并逆转了 MI 小鼠的细胞凋亡。从机制上讲，在 Bim 的启动子区域有一个潜在的 Sox4 结合位点，在有或没有 H ₂ O _{2 的}培养心肌细胞中，Sox4 的强制表达显着促进了 Bim 的表达，而敲除 Sox4 则抑制了 Bim 的表达。进一步的研究表明，沉默 Bim 减弱了 Sox4 诱导的心肌细胞凋亡，表明 Sox4 通过调节 Bim 表达促进心肌细胞凋亡，可作为 MI 的潜在治疗靶点。

更新日期：2020-07-13

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