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学科主题: 基础医学
题名:
C1q/tumor necrosis factor-related protein-6 attenuates post-infarct cardiac fibrosis by targeting RhoA/MRTF-A pathway and inhibiting myofibroblast differentiation
作者: 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
发表日期: 2015-07-01
DOI: 10.1007/s00395-015-0492-7
卷: 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
所属项目编号: 81270158 ; 81470398 ; 81370192
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000357653100002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66471
Appears in Collections:基础医学院_心血管所_期刊论文

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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

Recommended Citation:
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).
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