title: Transforming growth factor-beta induces skeletal muscle atrophy and fibrosis through the induction of atrogin-1 and scleraxis.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopaedic Surgery, University of Michigan, 109 Zina Pitcher Place, BSRB 2017, Ann Arbor, Michigan 48109, USA. cmendias@umich.edu
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Mendias
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Gumucio
authors.forename: Max E
authors.initials: ME
authors.lastname: Davis
authors.forename: Caleb W
authors.initials: CW
authors.lastname: Bromley
authors.forename: Carol S
authors.initials: CS
authors.lastname: Davis
authors.forename: Susan V
authors.initials: SV
authors.lastname: Brooks
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D005355:Fibrosis / Q000139:chemically induced; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000187:drug effects; D009124:Muscle Proteins / Q000378:metabolism*; D009133:Muscular Atrophy / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000633:toxicity*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D024042:Collagen Type I; D049452:Green Fluorescent Proteins; D009124:Muscle Proteins; D044843:SKP Cullin F-Box Protein Ligases; D016212:Transforming Growth Factor beta; C503815:Scx protein, mouse; C486691:Fbxo32 protein, mouse