Transforming growth factor-β and fibrosis

被引:431
作者
Verrecchia, Franck [1 ]
Mauviel, Alain [1 ]
机构
[1] Hop St Louis, INSERM, U697, F-75010 Paris, France
关键词
collagen; connective tissue growth factor; fibrosis; Smad; transforming growth factor-beta;
D O I
10.3748/wjg.v13.i22.3056
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Transforming growth factor-beta (TGF-beta), a prototype of multifunctional cytokine, is a key regulator of extracellular matrix (ECM) assembly and remodeling. Specifically, TGF-beta isoforms have the ability to induce the expression of ECM proteins in mesenchymal cells, and to stimulate the production of protease inhibitors that prevent enzymatic breakdown of the ECM. Elevated TGF-beta expression in affected organs, and subsequent deregulation of TGF-beta functions, correlates with the abnormal connective tissue deposition observed during the onset of fibrotic diseases. During the last few years, tremendous progress has been made in the understanding of the molecular aspects of intracellular signaling downstream of the TGF-beta receptors. In particular, Smad proteins, TGF-beta receptor kinase substrates that translocate into the cell nucleus to act as transcription factors, have been studied extensively. The role of Smad3 in the transcriptional regulation of type I collagen gene expression and in the development of fibrosis, demonstrated both in vitro and in animal models with a targeted deletion of Smad3, is of critical importance because it may lead to novel therapeutic strategies against these diseases. This review focuses on the mechanisms underlying Smad modulation of fibrillar collagen expression and how it relates to fibrotic processes. (c) 2007 The WJG Press. All rights reserved.
引用
收藏
页码:3056 / 3062
页数:7
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