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

✍ Scribed by Christopher L. Mendias; Jonathan P. Gumucio; Max E. Davis; Caleb W. Bromley; Carol S. Davis; Susan V. Brooks

• Book ID: 102538039
• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 121 KB
• Volume: 45
• Category: Article
• ISSN: 0148-639X
• DOI: 10.1002/mus.22232

✦ Synopsis

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