Myostatin directly regulates skeletal muscle fibrosis

Bo Li Zhao, Helen D. Kollias, Kathryn Rae Wagner

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)19371-19378
Number of pages8
JournalJournal of Biological Chemistry
Volume283
Issue number28
DOIs
StatePublished - Jul 11 2008

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Myostatin
Muscle
Skeletal Muscle
Fibrosis
Muscles
Fibroblasts
Extracellular Matrix Proteins
p38 Mitogen-Activated Protein Kinases
Muscular Diseases
Growth
Muscle Cells
Regeneration
Collagen
Chemical activation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Myostatin directly regulates skeletal muscle fibrosis. / Zhao, Bo Li; Kollias, Helen D.; Wagner, Kathryn Rae.

In: Journal of Biological Chemistry, Vol. 283, No. 28, 11.07.2008, p. 19371-19378.

Research output: Contribution to journalArticle

Zhao, Bo Li ; Kollias, Helen D. ; Wagner, Kathryn Rae. / Myostatin directly regulates skeletal muscle fibrosis. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 28. pp. 19371-19378.
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