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Heat shock transcription factor 1 protects against pressure overload-induced cardiac fibrosis via Smad3 期刊论文

编号：

65621885-c67e-4bf3-a466-82b70988f551
作者：

Zhou, Ning^[1];Ye, Yong^[2,3];Wang, Xingxu^[2,3];Ma, Ben^[4];Wu, Jian^[2,3];Li, Lei^[2,3];Wang, Lin^[1];Wang, Dao Wen^[1];Zou, Yunzeng(邹云增)*^[2,3]
语种：

English
期刊：

JOURNAL OF MOLECULAR MEDICINE-JMM ISSN：0946-2716 2017 年 95 卷 4 期 (445 - 460) ; APR
收录：
关键词：

Pressure overload Cardiac fibrosis Heat shock transcription factor 1 Smad3 Cardiac dysfunction Fibroblasts
摘要：

Fibrotic cardiac muscle exhibits high stiffness and low compliance which are major risk factors of heart failure. Although heat shock transcription factor 1 (HSF1) was identified as an intrinsic cardioprotective factor, the role that HSF1 plays in cardiac fibrosis remains unclear. Our study aims to investigate the role of HSF1 in pressure overload-induced cardiac fibrosis and the underlying mechanism. HSF1 phosphorylation was significantly downregulated in transverse aortic constriction (TAC)-treated mouse hearts and mechanically stretched cardiac fibroblasts (cFBs). HSF1 transgenic (TG) mice, HSF1 deficient heterozygote (KO) mice, and their wild-type littermates were subjected to sham or TAC surgery for 4 weeks. HSF1 overexpression significantly attenuated pressure overload-induced cardiac fibrosis and dysfunction. Conversely, HSF1 KO mice showed deteriorated fibrotic response and cardiac dysfunction upon TAC. Moreover, we uncovered that overexpression of HSF1 protected against fibrotic response of cFBs to pressure overload. Mechanistically, we observed that the phosphorylation and the nuclear distribution of the Smad family member 3 (Smad3) were significantly decreased in HSF1-overexpressing mouse hearts, while being greatly increased in HSF1 KO mouse hearts upon TAC, compared to the control hearts, respectively. Similar alteration of Smad3 phosphorylation and nuclear distribution were found in isolated mouse cardiac fibroblasts and mechanically stretched cFBs. Constitutively active Smad3 blocked the anti-fibrotic effect of HSF1 in cFBs. Furthermore, we found a direct binding of phosphorylated HSF1 and Smad3, which can be suppressed by mechanical stress. In conclusion, the present study demonstrated for the first time that HSF1 acts as a novel negative regulator of cardiac fibrosis by blocking Smad3 activation.
推荐引用方式
GB/T 7714：

Zhou Ning,Ye Yong,Wang Xingxu, et al. Heat shock transcription factor 1 protects against pressure overload-induced cardiac fibrosis via Smad3 [J].JOURNAL OF MOLECULAR MEDICINE-JMM,2017,95(4):445-460.
APA：

Zhou Ning,Ye Yong,Wang Xingxu,Ma Ben,&Zou Yunzeng.(2017).Heat shock transcription factor 1 protects against pressure overload-induced cardiac fibrosis via Smad3 .JOURNAL OF MOLECULAR MEDICINE-JMM,95(4):445-460.
MLA：

Zhou Ning, et al. "Heat shock transcription factor 1 protects against pressure overload-induced cardiac fibrosis via Smad3" .JOURNAL OF MOLECULAR MEDICINE-JMM 95,4(2017):445-460.

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