| First Author | Choi HI | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 8751 |
| PubMed ID | 31217524 | Mgi Jnum | J:281289 |
| Mgi Id | MGI:6357301 | Doi | 10.1038/s41598-019-45347-0 |
| Citation | Choi HI, et al. (2019) Peroxiredoxin V (PrdxV) negatively regulates EGFR/Stat3-mediated fibrogenesis via a Cys48-dependent interaction between PrdxV and Stat3. Sci Rep 9(1):8751 |
| abstractText | Activation of the epidermal growth factor receptor (EGFR)/signal transducer and activator of 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 the activity of Stat3 in TGF-beta-treated NRK49F cells. However, the underlying mechanism of PrdxV remains poorly understood. To investigate molecular mechanism of PrdxV, we used a transgenic mouse model expressing PrdxV siRNA (PrdxV(si) mice) and performed unilateral ureteral obstruction (UUO) for 7 days. 209/MDCT cells were transiently transfected with HA-tagged WT PrdxV and C48S PrdxV. Transgenic PrdxV(si) mice displayed an exacerbated epithelial-to-mesenchymal transition (EMT) as well as an increase in oxidative stress induced by UUO. In the UUO kidney of the PrdxV(si) mouse, knockdown of PrdxV increased Tyr1068-specific EGFR and Stat3 phosphorylation, whereas overexpression of WT PrdxV in 209/MDCT cells showed the opposite results. Immunoprecipitation revealed the specific interaction between WT PrdxV and Stat3 in the absence or presence of TGF-beta stimulation, whereas no PrdxV-EGFR or C48S PrdxV-Stat3 interactions were detected under any conditions. In conclusion, PrdxV is an antifibrotic effector that sustains renal physiology. Direct interaction between PrdxV and Stat3 through Cys48 is a major molecular mechanism. |
