Myocardin-related transcription factors A and B are key regulators of TGF-β1-induced fibroblast to myofibroblast differentiation.
Myocardin-related transcription factors A and B are key regulators of TGF-β1-induced fibroblast to myofibroblast differentiation.
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DOI：
10.1038/jid.2011.219
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发表时间：
2011-12
影响因子：
6.5
通讯作者：
Tomasek, James J.
中科院分区：
文献类型：
--
作者：
Crider, Beverly J.;Risinger, George M., Jr.;Haaksma, Carol J.;Howard, Eric W.;Tomasek, James J.
肌成纤维细胞是一种可收缩的平滑肌样细胞，其特征是平滑肌α-肌动蛋白（SMαA）的重新表达，通常具有协助伤口愈合的功能，但也与病理性挛缩有关。转化生长因子β -1 （TGF-β1）有助于促进成纤维细胞向肌成纤维细胞的分化，但这种分化在TGF-β1的作用下发生的确切机制尚不清楚。心肌素相关转录因子-a和-B （mrtf, MRTF-A/B）是调节平滑肌细胞和成纤维细胞中平滑肌特异性细胞骨架蛋白（包括SMαA）表达的转录共激活因子。在这项研究中，我们证明TGF-β1通过mrtf的作用介导肌成纤维细胞分化和收缩基因程序的表达。瞬时转染组成活性的MRTF-A诱导SMαA和其他平滑肌特异性细胞骨架蛋白的表达增加，即使在没有TGF-β1的情况下，肌成纤维细胞的收缩性也会增加。在TGF-β1分化的肌成纤维细胞中，MRTF-A/B敲低导致平滑肌特异性细胞骨架蛋白表达水平降低，收缩力产生减少，局灶黏附大小和数量减少。这些结果提供了直接证据，证明mrtf是TGF-β1响应的肌成纤维细胞分化的介质。
Myofibroblasts are contractile, smooth muscle-like cells that are characterized by the de novo expression of smooth muscle α-actin (SMαA) and normally function to assist in wound closure, but have been implicated in pathological contractures. Transforming growth factor beta-1 (TGF-β1) helps facilitate the differentiation of fibroblasts into myofibroblasts, but the exact mechanism by which this differentiation occurs, in response to TGF-β1, remains unclear. Myocardin-related transcription factors-A and -B (MRTFs, MRTF-A/B) are transcriptional co-activators that regulate the expression of smooth muscle-specific cytoskeletal proteins, including SMαA, in smooth muscle cells and fibroblasts. In this study, we demonstrate that TGF-β1 mediates myofibroblast differentiation and the expression of a contractile gene program through the actions of the MRTFs. Transient transfection of a constitutively-active MRTF-A induced an increase in the expression of SMαA and other smooth muscle-specific cytoskeletal proteins, and an increase in myofibroblast contractility, even in the absence of TGF-β1. MRTF-A/B knockdown, in TGF-β1 differentiated myofibroblasts, resulted in decreased smooth muscle-specific cytoskeletal protein expression levels and reduced contractile force generation, as well as a decrease in focal adhesion size and number. These results provide direct evidence that the MRTFs are mediators of myofibroblast differentiation in response to TGF-β1.
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影响因子：
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作者：
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