Peroxiredoxin V (PrdxV) negatively regulates EGFR/Stat3-mediated fibrogenesis via a Cys48-dependent interaction between PrdxV and Stat3.

摘要: Activation of the epidermal growth factor receptor (EGFR)/signal transducer and activator transcription 3 (Stat3) signaling pathway has been reported to be associated with renal fibrosis. We have recently demonstrated that peroxiredoxin V (PrdxV) acted as an antifibrotic effector by inhibiting activity Stat3 in TGF-β-treated NRK49F cells. However, underlying mechanism PrdxV remains poorly understood. To investigate molecular PrdxV, we used a transgenic mouse model expressing siRNA (PrdxVsi mice) performed unilateral ureteral obstruction (UUO) for 7 days. 209/MDCT cells were transiently transfected HA-tagged WT C48S PrdxV. Transgenic PrdxVsi mice displayed exacerbated epithelial-to-mesenchymal transition (EMT) well increase oxidative stress induced UUO. In UUO kidney mouse, knockdown increased Tyr1068-specific EGFR phosphorylation, whereas overexpression showed opposite results. Immunoprecipitation revealed specific interaction between absence or presence TGF-β stimulation, no PrdxV-EGFR PrdxV-Stat3 interactions detected under any conditions. conclusion, is sustains physiology. Direct through Cys48 major mechanism.