期刊论文详细信息
Journal of Cellular and Molecular Medicine
Angiotensin II receptor type 1 blockade decreases CTGF/CCN2‐mediated damage and fibrosis in normal and dystrophic skeletal muscles
Claudio Cabello-Verrugio2  María Gabriela Morales2  Daniel Cabrera2  Carlos P. Vio1 
[1] Laboratorio de Fisiología, Centro de Regeneración y Envejecimiento (CARE), Departamento de Fisiología, Pontificia Universidad Católica de Chile, Santiago, Chile;Laboratorio de Diferenciación Celular y Patología, Centro de Regulación Celular y Patología (CRCP), Centro de Regeneración y Envejecimiento (CARE), Departamento de Biología Celular y Molecular, Pontificia Universidad Católica de Chile, Santiago, Chile
关键词: CTGF;    skeletal muscle fibrosis;    angiotensin II receptor type I blocker (ARB);    muscular dystrophies;   
DOI  :  10.1111/j.1582-4934.2011.01354.x
来源: Wiley
PDF
【 摘 要 】

Abstract

Connective tissue growth factor (CTGF/CCN-2) is mainly involved in the induction of extracellular matrix (ECM) proteins. The levels of CTGF correlate with the degree and severity of fibrosis in many tissues, including dystrophic skeletal muscle. The CTGF overexpression in tibialis anterior skeletal muscle using an adenoviral vector reproduced many of the features observed in dystrophic muscles including muscle damage and regeneration, fibrotic response and decrease in the skeletal muscle strength. The renin–angiotensin system is involved in the genesis and progression of fibrotic diseases through its main fibrotic components angiotensin-II and its transducer receptor AT-1. The use of AT-1 receptor blockers (ARB) has been shown to decrease fibrosis. In this paper, we show the effect of AT-1 receptor blockade on CTGF-dependent biological activity in skeletal muscle cells as well as the response to CTGF overexpression in normal skeletal muscle. Our results show that in myoblasts ARB decreased CTGF-mediated increase of ECM protein levels, extracellular signal regulated kinases 1/2 (ERK-1/2) phosphorylation and stress fibres formation. In tibialis anterior muscle overexpressing CTGF using an adenovirus, ARB treatment decreased CTGF-mediated increase of ECM molecules, α-SMA and ERK-1/2 phosphorylation levels. Quite remarkable, ARB was able to prevent the loss of contractile force of tibialis anterior muscles overexpressing CTGF. Finally, we show that ARB decreased the levels of fibrotic proteins, CTGF and ERK-1/2 phosphorylation augmented in a dystrophic skeletal muscle from mdx mice. We propose that ARB is a novel pharmacological tool that can be used to decrease the fibrosis induced by CTGF in skeletal muscle associated with muscular dystrophies.

【 授权许可】

Unknown   
© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd

【 预 览 】
附件列表
Files Size Format View
RO202107150012518ZK.pdf 1009KB PDF download
  文献评价指标  
  下载次数:0次 浏览次数:1次