Publication
Title
Angiotensin II type 1 receptor blockade attenuates TGF-beta-induced failure of muscle regeneration in multiple myopathic states
Author
Abstract
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.
Language
English
Source (journal)
Nature medicine. - London, 1995, currens
Publication
London : 2007
ISSN
1078-8956 [print]
1546-170X [online]
Volume/pages
13 :2 (2007) , p. 204-210
ISI
000244031700030
Full text (Publisher's DOI)
UAntwerpen
Publication type
Subject
External links
Web of Science
Record
Identifier
Creation 05.11.2018
Last edited 08.12.2021