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

Introduction: Transforming growth factor-beta (TGF-beta) is a well-known regulator of fibrosis and inflammation in many tissues. During embryonic development, TGF-beta signaling induces expression of the transcription factor scleraxis, which promotes fibroblast proliferation and collagen synthesis in tendons. In skeletal muscle, TGF-beta has been shown to induce atrophy and fibrosis, but the effect of TGF-beta 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-beta and measured force production, scleraxis, procollagen Ia2, and atrogin-1 protein levels. Results: TGF-beta decreased muscle fiber size and dramatically reduced maximum isometric force production. TGF-beta also induced scleraxis expression in muscle fibroblasts, and increased procollagen Ia2 and atrogin-1 levels in muscles. Conclusion: These results provide new insight into the effect of TGF-beta on muscle contractility and the molecular mechanisms behind TGF-beta mediated muscle atrophy and fibrosis. Muscle Nerve 45: 5559, 2012