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- Title
Angiotensin II type 1 receptor blockade attenuates TGF-beta-induced failure of muscle regeneration in multiple myopathic states.
- Authors
Cohn, Ronald D; van Erp, Christel; Habashi, Jennifer P; Soleimani, Arshia A; Klein, Erin C; Lisi, Matthew T; Gamradt, Matthew; ap Rhys, Colette M; Holm, Tammy M; Loeys, Bart L; Ramirez, Francesco; Judge, Daniel P; Ward, Christopher W; Dietz, Harry C
- Abstract
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)-beta (refs. 2,3). TGF-beta is a known inhibitor of terminal differentiation of cultured myoblasts; however, the functional contribution of TGF-beta signaling to disease pathogenesis in various inherited myopathic states in vivo remains unknown. Here we show that increased TGF-beta activity leads to failed muscle regeneration in fibrillin-1-deficient mice. Systemic antagonism of TGF-beta through administration of TGF-beta-neutralizing antibody or the angiotensin II type 1 receptor blocker losartan normalizes muscle architecture, repair and function in vivo. Moreover, we show TGF-beta-induced failure of muscle regeneration and a similar therapeutic response in a dystrophin-deficient mouse model of Duchenne muscular dystrophy.
- Publication
Nature medicine, 2007, Vol 13, Issue 2, p204
- ISSN
1078-8956
- Publication type
Journal Article
- DOI
10.1038/nm1536