Transforming growth factor-beta induces skeletal muscle atrophy and fibrosis through the induction of atrogin-1 and scleraxis.
Transforming growth factor-beta induces skeletal muscle atrophy and fibrosis through the induction of atrogin-1 and scleraxis.
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DOI：
10.1002/mus.22232
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发表时间：
2012-01
期刊：
影响因子：
3.4
通讯作者：
Brooks, Susan V.
中科院分区：
文献类型：
--
作者：
Mendias, Christopher L.;Gumucio, Jonathan P.;Davis, Max E.;Bromley, Caleb W.;Davis, Carol S.;Brooks, Susan V.
转化生长因子-β(TGFR-β)是许多组织中公认的纤维化和炎症调节因子。在胚胎发育过程中，转化生长因子-β信号诱导转录因子硬化轴的表达，促进肌腱成纤维细胞的增殖和胶原的合成。在骨骼肌中，转化生长因子-β可诱导肌肉萎缩和纤维化，但转化生长因子-β对肌肉收缩和硬化轴表达的影响以及肌肉萎缩的重要调节因子--萎缩素-1的作用尚不清楚。我们用转化生长因子-β处理小鼠的肌肉，并检测力量产生、硬化症、前胶原Iα2和阿托金-1蛋白水平。转化生长因子-β减少了肌肉纤维的大小，并显著减少了最大等长力的产生。转化生长因子-β还可诱导成纤维细胞硬化轴的表达，增加肌肉中前胶原I、α-2和阿托金-1的水平。这些结果为了解转化生长因子-β对肌肉收缩的影响以及转化生长因子-β介导的肌肉萎缩和纤维化的分子机制提供了新的见解。
Transforming growth factor-beta (TGF-β) is a well known regulator of fibrosis and inflammation in many tissues. During embryonic development, TGF-β signaling induces the expression of the transcription factor scleraxis which promotes fibroblast proliferation and collagen synthesis in tendons. In skeletal muscle, TGF-β has been shown to induce atrophy and fibrosis, but the effect of TGF-β on muscle contractility and the expression of scleraxis and atrogin-1, an important regulator of muscle atrophy, were not known. We treated muscles from mice with TGF-β and measured force production, and scleraxis, procollagen Iα2 and atrogin-1 protein levels. TGF-β decreased muscle fiber size and dramatically reduced maximum isometric force production. TGF-β also induced scleraxis expression in muscle fibroblasts, and increased procollagen Iα2 and atrogin-1 levels in muscles. These results provide new insight into the effect of TGF-β on muscle contractility and the molecular mechanisms behind TGF-β-mediated muscle atrophy and fibrosis.
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