Oxidative stress and glutathione in TGF-β-mediated fibrogenesis

Abstract

Transforming growth factor beta (TGF-β) 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-β increases ROS production and decreases the concentration of glutathione (GSH), the most abundant intracellular free thiol and an important antioxidant, in various types of cells, which mediates many of TGF-β’s fibrogenic effects. 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 (NAC), 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 TGF-β’s fibrogenesis and the potential therapeutic values of antioxidant treatment in fibrotic diseases.

Intracellular redox equilibrium is essential for the constitutive expression of AP-1 dependent genes in resting cells: Studies on TGF-β1 regulation

“…Previous reports have showed that ROS can regulate TGF-β1 synthesis GONZÁLEZ-RAMOS ET AL. 4 (5,12,17,23,25,32) also through the activation of the transcription factor AP-1 (12). Taking into account this fact, we hypothesized that basal concentrations of ROS could be involved in the constitutive expression of TGF-β1.…”

Effect of <i>Phellodendron chinense</i> Extract on Carrageenan- Induced Chronic Prostatitis in Rats

“…TGF-β is the most extensively studied molecule in fibrosis and stimulates the production of reactive oxygen species (ROS) in various types of cells, whereas ROS activated TGF-β and mediate many of the fibrogenic effects of TGF-β [22]. TGF-β1 is known to induce fibroblast differentiation of into myofibroblast/smooth muscle cell in the human prostate [23].…”

Oxidative stress in subsynovial connective tissue of idiopathic carpal tunnel syndrome

“…23,24 Various cytokines and growth factors are involved in the development of fibrosis; however, TGF-␤ is considered to be the most potent and ubiquitous profibrogenic cytokine. 25 TGF-␤ induces fibrosis via the stimulation of fibroblast proliferation and activation. 26 TGF-␤ also upregulates the expression of extracellular matrix (ECM) proteins, which leads to increased ECM production and reduced ECM degradation.…”

“…TGF-␤ increase ROS production in numerous types of nonphagocytic cells, such as endothelial cells, epithelial cells, smooth muscle cells, and fibroblasts. 25,27,28 In addition to stimulating ROS production directly, TGF-␤ increases ROS levels by suppressing the expression of several antioxidant enzymes. 25,29 ROS also activates latent TGF-␤ and induces TGF-␤ gene expression.…”

“…25,27,28 In addition to stimulating ROS production directly, TGF-␤ increases ROS levels by suppressing the expression of several antioxidant enzymes. 25,29 ROS also activates latent TGF-␤ and induces TGF-␤ gene expression. 25 TGF-␤ is secreted as a latent form in which TGF-␤ homodimers are noncovalently associated with homodimers of their respective pro-peptide called the latency-associated peptide (LAP).…”