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TGF-β decreases intracellular GSH by suppressing the expression of glutamate cysteine ligase (GCL), the rate-limiting enzyme in de novo GSH synthesis. On the other hand, GSH suppresses TGF-β-induced fibrogenic effects by reducing intracellular ROS levels and by preventing oxidative modifications/inactivation of MAPK phosphatases and thus MAPK activation. GSH may also block TGF-β-induced Smad pathway activity indirectly by inhibiting MAPK pathways.
