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Letter
Nature Medicine 13, 204 - 210 (2007)
Published online: 21 January 2007 | Corrected online: 27 February 2007 | doi:10.1038/nm1536
There is a Corrigendum (April 2007) associated with this Letter.
Angiotensin II type 1 receptor blockade attenuates TGF-
–induced failure of muscle regeneration in multiple myopathic states
Ronald D Cohn1,2, Christel van Erp1, Jennifer P Habashi2,3, Arshia A Soleimani1, Erin C Klein1, Matthew T Lisi1, Matthew Gamradt1, Colette M ap Rhys1,2, Tammy M Holm1, Bart L Loeys1, Francesco Ramirez4, Daniel P Judge5, Christopher W Ward6 & Harry C Dietz1,2
Abstract
Skeletal muscle has the ability to achieve rapid repair in response to injury or disease1. 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)-
(refs. 2,3). TGF- is a known inhibitor of terminal differentiation of cultured myoblasts; however, the functional contribution of TGF- signaling to disease pathogenesis in various inherited myopathic states in vivo remains unknown4, 5. Here we show that increased TGF- activity leads to failed muscle regeneration in fibrillin-1–deficient mice. Systemic antagonism of TGF- through administration of TGF-–neutralizing antibody or the angiotensin II type 1 receptor blocker losartan normalizes muscle architecture, repair and function in vivo. Moreover, we show TGF-–induced failure of muscle regeneration and a similar therapeutic response in a dystrophin-deficient mouse model of Duchenne muscular dystrophy.
NOTE: In the version of this article initially published, the same panels were inadvertently used to show negative pSmad2/3 and periostin staining in muscle of Fbn1C1039G/+ mice treated with TGF--neutralizing antibody in both the steady-state (Fig. 1a, right column, second and third rows, respectively) and muscle-regeneration (Fig. 1b, right column, third and fourth rows, respectively) experiments. In reality, these images only relate to the steady-state experiment (Fig. 1a). The intended images for Figure 1b are provided (red, pSmad2/3 staining; green, periostin staining). As both sets of images show negative staining in neutralizing antibody–treated Fbn1C1039G/+ mice, this does not alter any observations or conclusions discussed in the manuscript. The error has been corrected in the HTML and PDF versions of the article.
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