Fibroblast growth factor 21 inhibited inflammation and fibrosis after myocardial infarction via EGR1
Fibroblast growth factor 21 inhibited inflammation and fibrosis after myocardial infarction via EGR1
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成纤维细胞生长因子21通过EGR1抑制心肌梗死后的炎症和纤维化
DOI：
10.1016/j.ejphar.2021.174470
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发表时间：
2021-11-05
影响因子：
5
通讯作者：
Wang, Ning
中科院分区：
文献类型：
--
作者：
Li, Jiamin;Gong, Liling;Wang, Ning
心肌梗死后心肌纤维化是心肌的自我修复过程，使心室重构难以逆转并持续发展。成纤维细胞生长因子21（FGF 21）在心血管和代谢性疾病中起重要作用。然而，FGF 21对心肌损伤引起的心肌炎症和纤维化的作用及其机制的研究却鲜有报道。使用超声心动图和苏木精-伊红和Masson三色染色评估给予或不给予重组人碱性FGF 21（rhbFGF 21）的成年雄性Sprague-Dawley大鼠，以确定心脏功能和心脏炎症和纤维化水平。FGF 21可能改善心脏重塑，其特征在于一系列炎症和纤维化相关因子的表达减少。此外，当FGF受体（FGFR）被阻断时，FGF 21的作用消失。从机制上讲，我们发现氧化应激诱导早期生长反应蛋白1（EGR 1）的下调，这有助于炎症因子和纤维化的减少与H2 O2处理的心肌细胞。总之，FGF 21通过调节FGFR-EGR 1有效地抑制了梗死后心脏中的炎症和纤维化。
Myocardial fibrosis in post-myocardial infarction is a self-healing process of the myocardium, making ventricular remodelling difficult to reverse and develop continuously. Fibroblast growth factor 21 (FGF21) plays an essential role in cardiovascular and metabolic diseases. However, the effect and mechanism of FGF21 action on cardiac inflammation and fibrosis caused by myocardial injury have rarely been reported. Adult male Sprague-Dawley rats administered with or without recombinant human basic FGF21 (rhbFGF21) were assessed using echocardiography and haematoxylin-eosin and Masson's trichrome staining to determine the cardiac function and cardiac inflammation and fibrosis levels. FGF21 might improve cardiac remodelling, as characterised by a decrease in the expression of a series of inflammatory and fibrosis-related factors. Moreover, when FGF receptors (FGFRs) were blocked, the effects of FGF21 disappeared. Mechanistically, we found that oxidative stress induced the downregulation of early growth response protein 1 (EGR1), which contributed to inflammatory factors and fibrosis reduction in cardiomyocytes treated with H2O2. Collectively, FGF21 effectively suppressed the inflammation and fibrosis in post-infarcted hearts by regulating FGFR-EGR1.