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

Authors

  • Christopher L. Mendias PhD,

    Corresponding author
    1. Department of Orthopaedic Surgery, University of Michigan, 109 Zina Pitcher Place, BSRB 2017, Ann Arbor, Michigan 48109, USA
    • Department of Orthopaedic Surgery, University of Michigan, 109 Zina Pitcher Place, BSRB 2019, Ann Arbor, Michigan 48109, USA
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  • Jonathan P. Gumucio BS,

    1. Department of Orthopaedic Surgery, University of Michigan, 109 Zina Pitcher Place, BSRB 2017, Ann Arbor, Michigan 48109, USA
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  • Max E. Davis,

    1. Department of Orthopaedic Surgery, University of Michigan, 109 Zina Pitcher Place, BSRB 2017, Ann Arbor, Michigan 48109, USA
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  • Caleb W. Bromley,

    1. Department of Orthopaedic Surgery, University of Michigan, 109 Zina Pitcher Place, BSRB 2017, Ann Arbor, Michigan 48109, USA
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  • Carol S. Davis BS,

    1. Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA
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  • Susan V. Brooks PhD

    1. Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA
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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. Muscle Nerve 45: 55–59, 2012

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