The Role of TGF-β1/Smads Signaling Pathway in Anti-myocardial Fibrosis Effect of SIRT1 and Related Mechanism
10.3870/j.issn.1672-0741.23.04.017
- VernacularTitle:TGF-β1/Smads信号通路在SIRT1抗心肌纤维化中的作用及机制研究
- Author:
Ting HE
1
;
Jun CHEN
;
Mu PANG
Author Information
1. 深圳市中医院,广州中医药大学第四临床医学院药学部,深圳 518033
- Keywords:
SIRT1;
pressure overload;
myocardial fibrosis;
TGF-β1/Smads signaling pathway
- From:
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong
2024;53(1):45-51
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effect of sirtuin 1(SIRT1)on rat myocardial fibrosis induced by pressure overload and the proliferation of cardiac fibroblasts induced by angiotensin Ⅱ(Ang Ⅱ),and to explore the molecular mechanisms.Methods The pressure overload-induced myocardial fibrosis was established by abdominal aorta constriction(AAC)procedure in vi-vo.After treatment with SIRT1 activator,the myocardial interstitial fibrosis and the collagen volume fraction were evaluated by Masson's trichrome staining.The protein expressions of TGF-β1/Smads were determined by immunohistochemical analy-sis.After in vitro intervention of Ang Ⅱ or Ang Ⅱ with SIRT1 activator,the fibroblasts proliferation was detected by MTT as-say.The mRNA and protein expressions of collagen Ⅰ/Ⅲ(Col1α1/3α1),SIRT1 and TGF-β1/Smads in myocardial tissue and fi-broblasts were evaluated by qRT-PCR and Western blotting.Results Compared with the sham operation group,myocardial in-terstitial fibrosis was significantly observed in the pressure overload model group,myocardial collagen volume fraction was in-creased,expressions of Col1α1/3α1 and TGF-β1/Smads were significantly increased,and SIRT1 expression was decreased.After the intervention of SRT1720,SIRT1 activator could improve the myocardial interstitial fibrosis induced by pressure overload,downregulate the expressions of Col1α1/3α1 and TGF-β1/Smads,and upregulate the expression of SIRT1.Meanwhile,correla-tion analysis showed that the protein expression of SIRT1 was negatively correlated with the expression of TGF-β1.In addition,SRT1720 also inhibited Ang Ⅱ-induced fibroblast proliferation and increased expression of Col1α1/3α1 and TGF-β1.Conclusion Activation of SIRT1 inhibits pressure overload-induced myocardial fibrosis and Ang Ⅱ-induced fibroblasts proliferation via regu-lation of the TGF-β1/Smads signaling pathway.
