Glutathione redox regulates TGF-beta-induced fibrogenic effects through Smad3 activation.
Transforming growth factor-beta (TGF-beta) plays a pivotal role in the fibrogenic action involved in the induction 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-beta1-induced phosphorylation of Smad3, while inhibiting TGF-beta1-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.
Ono
Akihiro
A
Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-machi, Maebashi 371-8511, Japan.
Utsugi
Mitsuyoshi
M
Masubuchi
Ken
K
Ishizuka
Tamotsu
T
Kawata
Tadayoshi
T
Shimizu
Yasuo
Y
Hisada
Takeshi
T
Hamuro
Junji
J
Mori
Masatomo
M
Dobashi
Kunio
K
D000199:Actins / Q000096:biosynthesis; D002460:Cell Line; D024042:Collagen Type I / Q000096:biosynthesis; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D032446:Myoblasts / Q000378:metabolism; D010766:Phosphorylation; D011658:Pulmonary Fibrosis / Q000378:metabolism*; D051900:Smad3 Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
C541116:ACTA2 protein, human; D000199:Actins; C526317:CCN2 protein, human; D024042:Collagen Type I; D005353:Fibronectins; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D055513:Connective Tissue Growth Factor; D003907:Dexamethasone; D005978:Glutathione