TET2在心肌纤维化中的作用初探

The Role of TET2 in Myocardial Fibrosis in Mice

探究TET2在异丙肾上腺素(ISO)诱导的小鼠心肌纤维化中的作用及机制。构建ISO构建的TET2敲除小鼠和野生型小鼠模型,Western blot检测心肌组织中TGF-β1/Smad3、Collagen1和Collagen3的表达,HE及马松染色检测心肌组织病理学改变,心脏超声评估心功能。TET2在ISO诱导的小鼠心肌组织中表达显著升高;在心肌纤维化模型中,TET2敲除小鼠较野生型小鼠心功能下降,心肌组织中TGF-β1/Smad3、Collagen1和Collagen3表达升高,同时HE及马松染色示TET2敲除小鼠心肌纤维化加重。TET2通过TGF-β1/Smad3信号通路参与小鼠心肌纤维化。

Heart failure is the final stage of various cardiovascular diseases.Pathological myocardial remodeling caused by myocardial fibrosis is an important cause of the occurrence and development of heart failure.Epigenetic mechanisms are involved in the regula⁃tion of myocardial fibrosis.DNA methylation,as the most common epigenetic regulation mechanism,plays an important role in a variety of cardiovascular diseases,and TET2 is involved in the regulation of a variety of heart diseases by demethylation.To explore the role and mechanism of TET2 in myocardial fibrosis induced by isoproterenol(ISO)in mice,the authors constructed TET2 knock⁃out mice and wild type mice models by ISO.The expressions of TGF⁃β1/Smad3,Collagen1 and Collagen3 in myocardial tissue were detected by Western blot,the pathological changes of myocardial tissue were detected by HE and Masson staining,and the cardiac function was evaluated by echocardiography.The authors observed the expression of TET2 was significantly increased in ISO⁃induced mouse myocardial tissue.In the myocardial fibrosis model,the cardiac function of TET2 knockout mice was lower than that of wild type mice,and the expressions of TGF⁃β1/Smad3,Collagen1 and Collagen3 in myocardial tissue were increased.HE and Masson staining showed that TET2 knockout mice had aggravated myocardial fibrosis.This study confirmed that TET2 knockout aggravates ISO⁃induced myocardial fibrosis in mice.TET2 knockout enhances the TGF⁃β1/Smad3 signaling pathway,activates the expression of Collagen1 and Collagen3,aggravates myocardial fibrosis and leads to the decline of cardiac function.This result suggests that TET2 may play a role as a novel protective factor in the treatment and prevention of myocardial fibrosis.