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Title
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Angiotensin II type 1 receptor blockade attenuates TGF-beta-induced failure of muscle regeneration in multiple myopathic states
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Author
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Abstract
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| Skeletal muscle has the ability to achieve rapid repair in response to injury or disease(1). 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(4,5). 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. |
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Language
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English
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Source (journal)
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Nature medicine. - London, 1995, currens
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Publication
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London
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2007
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ISSN
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1078-8956
[print]
1546-170X
[online]
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DOI
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10.1038/NM1536
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Volume/pages
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13
:2
(2007)
, p. 204-210
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ISI
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000244031700030
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Full text (Publisher's DOI)
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