P eroxiredoxin 1 inhibits the oxidative stress induced apoptosis in renal tubulointerstitial fibrosis

Aim Apoptosis is one of the most important mechanisms underlying renal tubulointerstitial fibrosis. We identified a role of protein P eroxiredoxin 1 ( P rx1) in protecting apoptosis occurred in tubular epithelial cells of the rat and human kidney. Methods Immunohistochemistry ( IHC ) staining was used to detect P rx1 expression in kidney derived from unilateral‐ureteral obstruction ( UUO ) rats or patients with obstructive nephropathy. Modulation of P rx1 expression by transfecting siRNA and overexpression plasmid approach were carried out in NRK ‐52 E (rat kidney tubular epithelial cell line) cells. UUO ‐induced apoptosis was determined using TUNEL assay. Results Immunohistochemistry staining showed that P rx1 expressed in the cytoplasm of renal tubular epithelial cells, in the kidneys of UUO rats. The reduction was confirmed by both IHC and real‐time polymerase chain reaction following a course of renal tubulointerstitial fibrosis in UUO rats and a decrease of P rx1 occurred concomitantly with an elevation of TUNEL ‐positive cells. Fluorofenidone ( AKF‐PD ), a new anti‐tubulointerstitial fibrotic agent, attenuated P rx1 reduction in UUO rats. Furthermore, hydrogen peroxide ( H 2 O 2 )‐derived oxidative stress activated p38 MAPK , and induced apoptosis in NRK ‐52 E cells; knockdown of P rx1 sensitized both events in NRK ‐52 E cells, and overexpression of P rx1 diminished the apoptosis and the phosphorylation of p38 Conclusion Downregulation of P rx1 occurred in renal tubular epithelial cells of UUO rats and patients with obstructive nephropathy. P rx1 may alleviate the pathogenesis by inhibiting H 2 O 2 ‐induced apoptosis via inhibiting the p38 MAPK pathway. P rx1 may represent a useful target for a protective therapy towards renal tubulointerstitial fibrosis.