Li Zhao Bo, Kollias Helen D, Wagner Kathryn R
Department of Neurology and Neuroscience, The Johns Hopkins University, School of Medicine, Baltimore, Maryland 21287, USA.
J Biol Chem. 2008 Jul 11;283(28):19371-8. doi: 10.1074/jbc.M802585200. Epub 2008 May 3.
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.
骨骼肌纤维化是慢性肌病的主要病理标志，在慢性肌病中，肌纤维被肌肉成纤维细胞产生的胶原蛋白和其他细胞外基质蛋白的逐渐沉积所取代。最近的研究表明，在内源性肌肉生长调节因子肌肉生长抑制素缺失的情况下，肌肉的再生增强，相应地肌肉纤维化减少。我们现在证明，肌肉生长抑制素不仅调节肌细胞的生长，还直接调节肌肉成纤维细胞。我们的结果表明，肌肉生长抑制素在体外和体内均能刺激肌肉成纤维细胞的增殖以及细胞外基质蛋白的产生。此外，肌肉成纤维细胞表达肌肉生长抑制素及其假定的受体激活素受体IIB。由肌肉生长抑制素诱导的肌肉成纤维细胞增殖涉及Smad、p38丝裂原活化蛋白激酶（MAPK）和Akt信号通路的激活。这些结果扩展了我们对肌肉生长抑制素在肌肉组织中功能的理解，并为抗纤维化治疗提供了一个潜在靶点。
