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C1q/tumor necrosis factor-related protein-6 attenuates post-infarct cardiac fibrosis by targeting RhoA/MRTF-A pathway and inhibiting myofibroblast differentiation
Lei, Hong1,2; Wu, Dan1,2; Wang, Jin-Yu1,2; Li, Li1,2; Zhang, Cheng-Lin1,2; Feng, Han1,2; Fu, Feng-Ying1,2; Wu, Li-Ling1,2
关键词C1q/tumor Necrosis Factor-related Protein-6 Rhoa Myocardin-related Transcription Factor-a Myocardial Infarction Cardiac Fibrosis Myofibroblast Differentiation
刊名BASIC RESEARCH IN CARDIOLOGY
2015-07-01
DOI10.1007/s00395-015-0492-7
110期:4
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems
研究领域[WOS]Cardiovascular System & Cardiology
关键词[WOS]Ischemic Mouse Heart ; Myocardial-infarction ; Adiponectin Protects ; Ampk Activation ; Adipose-tissue ; Ppar-gamma ; Tnf-alpha ; Fibroblasts ; Expression ; Kinase
英文摘要

C1q/tumor necrosis factor-related protein-6 (CTRP6) is a newly identified adiponectin paralog with modulation effects on metabolism and inflammation. However, the cardiovascular function of CTRP6 remains unknown. This study aimed to determine its role in cardiac fibrosis and explore the possible mechanism. Myocardial infarction (MI) was induced by left anterior descending coronary artery ligation in rats. CTRP6 was mainly expressed in the cytoplasm of adult rat cardiomyocytes and significantly decreased in the border and infarct zones post-MI. Adenovirus-mediated CTRP6 delivery improved cardiac function, attenuated cardiac hypertrophy, alleviated cardiac fibrosis, and inhibited myofibroblast differentiation as well as the expression of collagen I, collagen III, and connective tissue growth factor post-MI. In cultured adult rat cardiac fibroblasts (CFs), exogenous or cardiomyocyte-secreted CTRP6 inhibited, whereas knockdown of CTRP6 facilitated transforming growth factor-beta 1 (TGF-beta 1)-induced expression of alpha-smooth muscle actin, smooth muscle 22 alpha, and profibrotic molecules. CTRP6 had no effect on CFs proliferation but attenuated CFs migration induced by TGF-beta 1. CTRP6 increased the phosphorylation of AMP-activated protein kinase (AMPK) and Akt in CFs and post-MI hearts. Pretreatment with adenine 9-beta-D-arabinofuranoside (AraA), an AMPK inhibitor, or LY294002, a phosphatidylinositol-3-kinase (PI3 K) inhibitor, abolished the protective effect of CTRP6 on TGF-beta 1-induced profibrotic response. Furthermore, CTRP6 had no effect on TGF-beta 1-induced Smad3 phosphorylation and nuclear translocation, whereas significantly decreased TGF-beta 1-induced RhoA activation and myocardin-related transcription factor-A (MRTF-A) nuclear translocation, and these effects were blocked by AMPK or Akt inhibition. In conclusion, CTRP6 attenuates cardiac fibrosis via inhibiting myofibroblast differentiation. AMPK and Akt activation are responsible for the CTRP6-mediated anti-fibrotic effect by targeting RhoA/MRTF-A pathway.

语种英语
WOS记录号WOS:000357653100002
通讯作者邮箱pathophy@bjmu.edu.cn
项目编号81270158 ; 81470398 ; 81370192
资助机构National Natural Science Foundation of China
引用统计
被引频次:10[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66471
专题北京大学基础医学院_心血管所
北京大学基础医学院
作者单位1.Peking Univ, Dept Physiol & Pathophysiol, Key Lab Mol Cardiovasc Sci, Minist Educ,Hlth Sci Ctr, Beijing 100191, Peoples R China
2.Peking Univ, Beijing Key Lab Cardiovasc Receptors Res, Hlth Sci Ctr, Beijing 100191, Peoples R China
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GB/T 7714
Lei, Hong,Wu, Dan,Wang, Jin-Yu,et al. C1q/tumor necrosis factor-related protein-6 attenuates post-infarct cardiac fibrosis by targeting RhoA/MRTF-A pathway and inhibiting myofibroblast differentiation[J]. BASIC RESEARCH IN CARDIOLOGY,2015,110(4).
APA Lei, Hong.,Wu, Dan.,Wang, Jin-Yu.,Li, Li.,Zhang, Cheng-Lin.,...&Wu, Li-Ling.(2015).C1q/tumor necrosis factor-related protein-6 attenuates post-infarct cardiac fibrosis by targeting RhoA/MRTF-A pathway and inhibiting myofibroblast differentiation.BASIC RESEARCH IN CARDIOLOGY,110(4).
MLA Lei, Hong,et al."C1q/tumor necrosis factor-related protein-6 attenuates post-infarct cardiac fibrosis by targeting RhoA/MRTF-A pathway and inhibiting myofibroblast differentiation".BASIC RESEARCH IN CARDIOLOGY 110.4(2015).
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