Skeletal muscle has the ability to achieve rapid repair in response to injury or disease. Many individuals with Marfan syndrome (MFS), caused by a deficiency of extracellular fibrillin-1, exhibit myopathy and often are unable to increase muscle mass despite physical exercise. Evidence suggests that selected manifestations of MFS reflect excessive signaling by transforming growth factor (TGF)-β (refs. 2,3). TGF-β is a known inhibitor of terminal differentiation of cultured myoblasts; however, the functional contribution of TGF-β signaling to disease pathogenesis in various inherited myopathic states in vivo remains unknown. Here we show that increased TGF-β activity leads to failed muscle regeneration in fibrillin-1-deficient mice. Systemic antagonism of TGF-β through administration of TGF-β-neutralizing antibody or the angiotensin II type 1 receptor blocker losartan normalizes muscle architecture, repair and function in vivo. Moreover, we show TGF-β-induced failure of muscle regeneration and a similar therapeutic response in a dystrophin-deficient mouse model of Duchenne muscular dystrophy. © 2007 Nature Publishing Group.
CITATION STYLE
Cohn, R. D., Van Erp, C., Habashi, J. P., Soleimani, A. A., Klein, E. C., Lisi, M. T., … Dietz, H. C. (2007). Angiotensin II type 1 receptor blockade attenuates TGF-β-induced failure of muscle regeneration in multiple myopathic states. Nature Medicine, 13(2), 204–210. https://doi.org/10.1038/nm1536
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