心肌细胞中SMAD4依赖的TGF-β信号对于维持成年心脏稳态至关重要。
Cardiomyocyte SMAD4-Dependent TGF-β Signaling is Essential to Maintain Adult Heart Homeostasis.
作者信息
Umbarkar Prachi, Singh Anand P, Gupte Manisha, Verma Vipin K, Galindo Cristi L, Guo Yuanjun, Zhang Qinkun, McNamara James W, Force Thomas, Lal Hind
机构信息
Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee.
出版信息
JACC Basic Transl Sci. 2019 Jan 16;4(1):41-53. doi: 10.1016/j.jacbts.2018.10.003. eCollection 2019 Feb.
The role of the transforming growth factor (TGF)-β pathway in myocardial fibrosis is well recognized. However, the precise role of this signaling axis in cardiomyocyte (CM) biology is not defined. In TGF-β signaling, SMAD4 acts as the central intracellular mediator. To investigate the role of TGF-β signaling in CM biology, the authors deleted SMAD4 in adult mouse CMs. We demonstrate that CM-SMAD4-dependent TGF-β signaling is critical for maintaining cardiac function, sarcomere kinetics, ion-channel gene expression, and cardiomyocyte survival. Thus, our findings raise a significant concern regarding the therapeutic approaches that rely on systemic inhibition of the TGF-β pathway for the management of myocardial fibrosis.
转化生长因子（TGF）-β信号通路在心肌纤维化中的作用已得到广泛认可。然而，该信号轴在心肌细胞（CM）生物学中的具体作用尚不清楚。在TGF-β信号传导中，SMAD4作为细胞内的核心介质。为了研究TGF-β信号在CM生物学中的作用，作者在成年小鼠CM中删除了SMAD4。我们证明，CM-SMAD4依赖性TGF-β信号对于维持心脏功能、肌节动力学、离子通道基因表达和心肌细胞存活至关重要。因此，我们的研究结果对依赖于全身抑制TGF-β信号通路来治疗心肌纤维化的方法提出了重大质疑。
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