Transforming growth factor-beta induces skeletal muscle atrophy and fibrosis through the induction of atrogin-1 and scleraxis

Muscle Nerve. 2012 Jan;45(1):55-9. doi: 10.1002/mus.22232.

Abstract

Introduction: 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 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.

Methods: We treated muscles from mice with TGF-β and measured force production, scleraxis, procollagen Iα2, and atrogin-1 protein levels.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Collagen Type I / metabolism
  • Fibrosis / chemically induced
  • Gene Expression Regulation / drug effects
  • Green Fluorescent Proteins / genetics
  • In Vitro Techniques
  • Mice
  • Mice, Transgenic
  • Muscle Contraction / drug effects
  • Muscle Proteins / metabolism*
  • Muscular Atrophy / chemically induced*
  • Muscular Atrophy / metabolism*
  • Muscular Atrophy / physiopathology
  • SKP Cullin F-Box Protein Ligases / metabolism*
  • Transforming Growth Factor beta / toxicity*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Collagen Type I
  • Muscle Proteins
  • Scx protein, mouse
  • Transforming Growth Factor beta
  • Green Fluorescent Proteins
  • Fbxo32 protein, mouse
  • SKP Cullin F-Box Protein Ligases