Myostatin directly regulates skeletal muscle fibrosis.
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.
Li
Zhao Bo
ZB
Department of Neurology and Neuroscience, The Johns Hopkins University, School of Medicine, Baltimore, Maryland 21287, USA.
Kollias
Helen D
HD
Wagner
Kathryn R
KR
D030301:Activin Receptors, Type II / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D051379:Mice; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D055435:Myostatin; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
C525912:Mstn protein, mouse; D055435:Myostatin; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D003094:Collagen; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D030301:Activin Receptors, Type II; C425584:activin receptor type II-B