Myostatin directly regulates skeletal muscle fibrosis
Myostatin directly regulates skeletal muscle fibrosis
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DOI：
10.1074/jbc.m802585200
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发表时间：
2008-07-11
影响因子：
4.8
通讯作者：
Wagner, Kathryn R.
中科院分区：
文献类型：
--
作者：
Li, Zhao Bo;Kollias, Helen D.;Wagner, Kathryn R.
骨骼肌纤维化是慢性肌病的主要病理学标志，其中肌纤维被肌成纤维细胞产生的胶原蛋白和其他细胞外基质蛋白的进行性沉积所取代。最近的研究表明，在缺乏内源性肌肉生长调节剂肌肉生长抑制素的情况下，肌肉的再生增强，并且肌肉纤维化相应地减少。我们现在证明，肌肉生长抑制素不仅调节肌细胞的生长，而且直接调节肌肉成纤维细胞。我们的研究结果表明，肌肉生长抑制素刺激肌肉成纤维细胞的增殖和生产的细胞外基质蛋白在体外和体内。此外，肌成纤维细胞表达肌生长抑制素及其推定受体激活素受体IIB。肌生长抑制素诱导的肌成纤维细胞增殖涉及Smad、p38 MAPK和Akt通路的激活。这些结果扩展了我们对肌生长抑制素在肌肉组织中的功能的理解，并为抗纤维化治疗提供了潜在的靶点。
Skeletal muscle fibrosis is a major pathological hallmark of chronic myopathies in which myofibers are replaced by progressive deposition of collagen and other extracellular matrix proteins produced by muscle fibroblasts. Recent studies have shown that in the absence of the endogenous muscle growth regulator myostatin, regeneration of muscle is enhanced, and muscle fibrosis is correspondingly reduced. We now demonstrate that myostatin not only regulates the growth of myocytes but also directly regulates muscle fibroblasts. Our results show that myostatin stimulates the proliferation of muscle fibroblasts and the production of extracellular matrix proteins both in vitro and in vivo. Further, muscle fibroblasts express myostatin and its putative receptor activin receptor IIB. Proliferation of muscle fibroblasts, induced by myostatin, involves the activation of Smad, p38 MAPK and Akt pathways. These results expand our understanding of the function of myostatin in muscle tissue and provide a potential target for anti-fibrotic therapies.