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

Transforming growth factor-β (TGF-β) 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-β 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-β1-induced phosphorylation of Smad3, while inhibiting TGF-β1-induced expressions of CTGF, collagen type1, fibronectin and transformation into myofibroblasts, which are characterized by the expression of α-smooth muscle actin. These data indicate that the intracellular glutathione redox status regulates TGF-β-induced fibrogenic effects through Smad3 activation.