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Smad6 complex 期刊论文

编号：

3a1481f7-c1c8-4401-a053-d412f50cb5df
作者：

Wang, Shijun;Sun, Aijun;Li, Lei;Zhao, Gang;Jia, Jianguo;Wang, Keqiang;Ge, Junbo(葛均波)*^[1,2]Zou, Yunzeng(邹云增)^[1,2]
语种：

English
期刊：

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE ISSN：1582-4934 2012 年 16 卷 10 期 (2301 - 2310) ; OCT
收录：
关键词：

BMP-2 TGF-ss 1 Smad6 Rho-associated kinase cardiac fibrosis
摘要：

Rho-associated kinase (ROCK) plays a critical role in pressure overload-induced left ventricular remodelling. However, the underlying mechanism remains unclear. Here, we reported that TGF-beta 1-induced ROCK elevation suppressed BMP-2 level and strengthened fibrotic response. Exogenous BMP-2 supply effectively attenuated TGF-beta 1 signalling pathway through Smad6-Smurf-1 complex activation. In vitro cultured cardiomyocytes, mechanical stretch up-regulated cardiac TGF-beta 1, TGF-beta 1-dependent ROCK and down-regulated BMP-2, but BMP-2 level could be reversed through blocking TGF-beta 1 receptor by SB-431542 or inhibition of ROCK by Y-27632. TGF-beta 1 could also activate ROCK and suppress endogenous BMP-2 level in a dose-dependent manner. Knock-down BMP-2 enhanced TGF-beta 1-mediated PKC-d and Smad3 signalling cascades. In contrast, treatment with Y-27632 or SB-431542, respectively suppressed ROCK-dependent PKC-d and Smad3 activation, but BMP-2 was only up-regulated by Y-27632. In addition, BMP-2 silencing abolished the effect of Y-27632, but not SB-431542 on suppression of TGF-beta 1 pathway. Further experiments showed that Smad6 Smurf1 interaction were required for BMP-2-evoked antagonizing effects. Smad6 overexpression attenuated TGF-beta 1-induced activation of PKC-d and Smad3, promoted TGF-beta RI degradation in BMP-2 knock-down cardiomyocytes, and could be abolished after knocking-down Smurf-1, in which Smad6/Smurf1 complex formation was critically involved. In vivo data showed that pressure overload-induced collagen deposition was attenuated, cardiac function was improved and TGF-beta 1-dependent activation of PKC-d and Smad3 was reduced after 2 weeks treatment with rhBMP-2(0.5 mg/kg) or Y-27632 (10 mg/kg) in mice that underwent surgical transverse aortic constriction. In conclusion, we propose that BMP-2, as a novel fibrosis antagonizing cytokine, may have potential beneficial effect in attenuating pressure overload-induced cardiac fibrosis.
推荐引用方式
GB/T 7714：

Wang Shijun,Sun Aijun,Li Lei, et al. Up-regulation of BMP-2 antagonizes TGF-beta 1/ROCK-enhanced cardiac fibrotic signalling through activation of Smurf1/Smad6 complex [J].JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2012,16(10):2301-2310.
APA：

Wang Shijun,Sun Aijun,Li Lei,Zhao Gang,&Zou Yunzeng.(2012).Up-regulation of BMP-2 antagonizes TGF-beta 1/ROCK-enhanced cardiac fibrotic signalling through activation of Smurf1/Smad6 complex .JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,16(10):2301-2310.
MLA：

Wang Shijun, et al. "Up-regulation of BMP-2 antagonizes TGF-beta 1/ROCK-enhanced cardiac fibrotic signalling through activation of Smurf1/Smad6 complex" .JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 16,10(2012):2301-2310.

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