CREG ameliorates the phenotypic switching of cardiac fibroblasts after myocardial infarction via modulation of CDC42.
CREG ameliorates the phenotypic switching of cardiac fibroblasts after myocardial infarction via modulation of CDC42.
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CREG 通过调节 CDC42 改善心肌梗死后心脏成纤维细胞的表型转换
DOI：
10.1038/s41419-021-03623-w
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发表时间：
2021-04-06
影响因子：
9
通讯作者：
Han Y
中科院分区：
文献类型：
--
作者：
Liu D;Tian X;Liu Y;Song H;Cheng X;Zhang X;Yan C;Han Y
心肌成纤维细胞向肌成纤维细胞的表型转换在心肌梗死后心肌纤维化中起重要作用。E1 A刺激基因的细胞阻遏物（CREG）保护血管紧张素II诱导的血管和心脏重塑。然而，CREG对心肌梗死后心脏成纤维细胞表型转换的影响和机制尚不清楚。本研究旨在探讨CREG在心肌梗死后心肌成纤维细胞表型转换中的作用及其机制。我们的研究结果表明，与同窝对照小鼠相比，CREG+/−小鼠在MI后第14天心脏功能恶化。心肌梗死后第14天，CREG+/−小鼠边缘区域的纤维化大小、αSMA和胶原蛋白-1表达增加。相反，外源性CREG蛋白在第14天显著改善C57 BL/6 J小鼠的心功能，抑制纤维化，并降低边缘区域αSMA和胶原-1的表达。CREG重组蛋白通过抑制细胞分裂控制蛋白42（CDC 42）的表达，抑制αSMA和胶原-1的表达，阻断缺氧诱导的心肌成纤维细胞增殖和迁移。我们的研究结果可能有助于建立新的策略的基础上澄清的关键分子CREG的作用，心肌梗死后的心脏成纤维细胞的表型转换。
Phenotype switching of cardiac fibroblasts into myofibroblasts plays important role in cardiac fibrosis following myocardial infarction (MI). Cellular repressor of E1A-stimulated genes (CREG) protects against vascular and cardiac remodeling induced by angiotensin-II. However, the effects and mechanisms of CREG on phenotype switching of cardiac fibroblasts after MI are unknown. This study aimed to investigate the role of CREG on the phenotype switching of cardiac fibroblasts following MI and its mechanism. Our findings demonstrated that, compared with littermate control mice, cardiac function was deteriorated in CREG+/−mice on day 14 post-MI. Fibrosis size, αSMA, and collagen-1 expressions were increased in the border regions of CREG+/−mice on day 14 post-MI. Conversely, exogenous CREG protein significantly improved cardiac function, inhibited fibrosis, and reduced the expressions of αSMA and collagen-1 in the border regions of C57BL/6J mice on day 14. In vitro, CREG recombinant protein inhibited αSMA and collagen-1 expression and blocked the hypoxia-induced proliferation and migration of cardiac fibroblasts, which was mediated through the inhibition of cell division control protein 42 (CDC42) expression. Our findings could help in establishing new strategies based on the clarification of the role of the key molecule CREG in phenotype switching of cardiac fibroblasts following MI.
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影响因子：
37.8
作者：
Liu W;Zi M;Naumann R;Ulm S;Jin J;Taglieri DM;Prehar S;Gui J;Tsui H;Xiao RP;Neyses L;Solaro RJ;Ke Y;Cartwright EJ;Lei M;Wang X
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Wang X
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5
作者：
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通讯作者：
Li, Shaohua
影响因子：
3.6
作者：
Sun, Li-ye;Zhao, Jin-chao;Bie, Zi-dong
通讯作者：
Bie, Zi-dong
影响因子：
37.8
作者：
Villalobos, Elisa;Criollo, Alfredo;Hill, Joseph A.
通讯作者：
Hill, Joseph A.
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影响因子：
8.3
作者：
Ye, Hongmei;Ling, Shukuan;Birnbaum, Yochai
通讯作者：
Birnbaum, Yochai