Glutathione redox regulates TGF-β-induced fibrogenic effects through Smad3 activation

被引:21
|
作者
Ono, Akihiro [1 ]
Utsugi, Mitsuyoshi [1 ]
Masubuchi, Ken [1 ]
Ishizuka, Tamotsu [1 ]
Kawata, Tadayoshi [1 ]
Shimizu, Yasuo [1 ]
Hisada, Takeshi [1 ]
Hamuro, Junji [2 ]
Mori, Masatomo [1 ]
Dobashi, Kunio [3 ]
机构
[1] Gunma Univ, Grad Sch Med, Dept Med & Mol Sci, Maebashi, Gunma 3718511, Japan
[2] Keio Univ, Sch Med, Dept Microbiol & Immunol, Tokyo, Japan
[3] Gunma Univ, Fac Med, Sch Hlth Sci, Maebashi, Gunma 3718511, Japan
关键词
Glutathione redox; Transforming growth factor-beta; Smad; Fibrogenic effect; Human lung fibroblast; Bronchial smooth muscle cell; TISSUE GROWTH-FACTOR; SMOOTH-MUSCLE CELLS; TRANSFORMING GROWTH-FACTOR-BETA-1; EXTRACELLULAR-MATRIX; EXPRESSION; BINDING; RANTES; MODEL; P38;
D O I
10.1016/j.febslet.2008.12.021
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Transforming growth factor-beta (TGF-beta) plays a pivotal role in the fibrogenic action involved in theinduction of connective tissue growth factor (CTGF), extracellular matrix and fibroblast transformation. Smad3 mediates TGF-beta signaling related to the fibrotic response. In human lung fibroblasts or bronchial smooth muscle cells, we demonstrated that an increase in the intracellular glutathione level suppressed TGF-beta 1-induced phosphorylation of Smad3, while inhibiting TGF-beta 1-induced expressions of CTGF, collagen type1, fibronectin and transformation into myofibroblasts, which are characterized by the expression of alpha-smooth muscle actin. These data indicate that the intracellular glutathione redox status regulates TGF-beta-induced fibrogenic effects through Smad3 activation. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
引用
收藏
页码:357 / 362
页数:6
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