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Transforming growth factor‐beta induces skeletal muscle atrophy and fibrosis through the induction of atrogin‐1 and scleraxis
Author(s) -
Mendias Christopher L.,
Gumucio Jonathan P.,
Davis Max E.,
Bromley Caleb W.,
Davis Carol S.,
Brooks Susan V.
Publication year - 2012
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.22232
Subject(s) - transforming growth factor , medicine , endocrinology , fibrosis , myostatin , contractility , skeletal muscle , muscle atrophy , atrophy , biology , transforming growth factor beta , growth factor , chemistry , microbiology and biotechnology , receptor
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