Figure 8.

Proposed model for antifibrotic effect of PrdxV. Under the pathological conditions such as UUO, UUO kidney increases the expression of TGF-β, a fibrotic cytokine, which promotes the activation of EGFR/Stat3, one of the noncanonical TGF-β signal pathways. In particular, the activation of Tyr1068 of EGFR serves as a docking site for the phosphorylation of Tyr705 of Stat3. Activated dimeric Stat3 increases the expression of fibrotic markers such as vimentin, which is regulated by stat3 in the nucleus, leading to renal fibrosis. In control kidney under normal physiological conditions, PrdxV binds to Stat3 in a catalytic Cys48-dependent manner and its binding plays a role in inhibiting the activation of EGFR/Stat3. Therefore, a decrease in PrdxV under fibrotic stress has an adverse effect on the maintenance of PrdxV-Stat3 interaction and leads to activation of the EGFR/Stat3 pathway.