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

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.