期刊
JOURNAL OF NEUROIMMUNOLOGY
卷 175, 期 1-2, 页码 77-86出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jneuroim.2006.03.005
关键词
muscular dystrophy; mdx animal model; muscle fibrosis; transforming growth factor-beta 1; fibrogenic cytokine; immunomodulation
Irreversible connective tissue proliferation in muscle is a pathological hallmark of Duchenne muscular dystrophy (DMD), a genetic degenerative muscle disease due to lack of the sarcolemmal protein dystrophin. Focal release of transforming growth factor-betal (TGF-beta 1) is involved in fibrosis development. Murine muscular dystrophy (mdx) is genetically homologous to DMD and histopathological alterations comparable to those in DMD muscles occur in diaphragm of older mdx mice. To investigate the early development of fibrosis and TGF-beta 1 involvement, we assessed diaphragms in 6-36-week-old mdx and C57/BL6 (control) mice for fibrosis, and used real-time PCR and ELISA to determine TGF-1 expression. Significantly greater fibrosis and TGF+beta 1 expression were found in mdx from the 6th week. Mice treated with neutralizing antibody against TGF+beta 1 had lower levels of TGF+beta 1 protein, reduced fibrosis, unchanged muscles fiber degeneration/ regeneration, but increased inflammatory cells (CD4+ lymphocytes). These data demonstrate early and progressive fibrosis in mdx diaphragm accompanied by TGF-beta 1 upregulation. Reduction of TGF-beta 1 appears promising as a therapeutic approach to muscle fibrosis, but further studies are required to evaluate long term effects of TGF-beta 1 immunomodulation on the immune system. (c) 2006 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据