Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructures and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China.
Biochem Biophys Res Commun. 2011 Apr 8;407(2):313-7. doi: 10.1016/j.bbrc.2011.03.008. Epub 2011 Mar 5.
Transforming growth factor β (TGF-β) signaling plays an important role in the pathogenesis of cardiac hypertrophy. However, the molecular mechanism of TGF-β signaling during the process of cardiac remodeling remains poorly understood. In the present study, by employing single-molecule fluorescence imaging approach, we demonstrated that in neonatal rat cardiomyocytes, TGF-β type II receptors (TβRII) existed as monomers at the low expression level, and dimerized upon TGF-β1 stimulation. Importantly, for the first time, we found the increased dimerization of TβRII in hypertrophic cardiomyocytes comparing to the normal cardiomyocytes. The enhanced TβRII dimerization was correlated with the enhanced Smad3 phosphorylation levels. These results provide new information on the mechanism of TGF-β signaling in cardiac remodeling.
转化生长因子 β(TGF-β)信号通路在心肌肥厚的发病机制中起着重要作用。然而,TGF-β信号在心脏重构过程中的分子机制仍知之甚少。在本研究中,我们采用单分子荧光成像方法,证明在新生大鼠心肌细胞中,TGF-β 型 II 受体(TβRII)在低表达水平时以单体形式存在,而在 TGF-β1 刺激下二聚化。重要的是,我们首次发现与正常心肌细胞相比,肥厚心肌细胞中 TβRII 的二聚化增加。增强的 TβRII 二聚化与 Smad3 磷酸化水平的增强相关。这些结果为 TGF-β 信号在心脏重构中的机制提供了新的信息。