Oxidative stress and glutathione in TGF-beta-mediated fibrogenesis.
Transforming growth factor beta (TGF-beta) is the most potent and ubiquitous profibrogenic cytokine, and its expression is increased in almost all the fibrotic diseases and in experimental fibrosis models. TGF-beta increases reactive oxygen species production and decreases the concentration of glutathione (GSH), the most abundant intracellular free thiol and an important antioxidant, which mediates many of the fibrogenic effects of TGF-beta in various types of cells. A decreased GSH concentration is also observed in human fibrotic diseases and in experimental fibrosis models. Although the biological significance of GSH depletion in the development of fibrosis remains obscure, GSH and N-acetylcysteine, a precursor of GSH, have been used in clinics for the treatment of fibrotic diseases. This review summarizes recent findings in the field to address the potential mechanism whereby oxidative stress mediates fibrogenesis induced by TGF-beta and the potential therapeutic value of antioxidant treatment in fibrotic diseases.
Department of Environmental Health Sciences, School of Public Health, Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. rliu@uab.edu
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Gaston Pravia
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D000975:Antioxidants; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D005978:Glutathione