title: Glutathione redox regulates TGF-beta-induced fibrogenic effects through Smad3 activation.
abstract: 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.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, 3-39-15, Showa-machi, Maebashi 371-8511, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ono
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Utsugi
authors.forename: Ken
authors.initials: K
authors.lastname: Masubuchi
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Ishizuka
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Kawata
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hisada
authors.forename: Junji
authors.initials: J
authors.lastname: Hamuro
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
authors.forename: Kunio
authors.initials: K
authors.lastname: Dobashi
mesh_terms: 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*
chemical_list: 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