Objective:To investigate the effect and mechanism of aminoacyl 4-hydroxylase A2(P4HA2)on renal interstitial fibrosis using in vivo and in vitro models.Methods:The ureteral ligation model was used to construct animal renal fibrosis,and the expression level of P4HA2 was detected by immuno-histochemistry;Different gradient concentrations of TGF-β were used to stimulate HK2 cells to con-struct a cellular renal fibrosis model,and the expression level of P4HA2 protein was detected by Western Blot and immunofluorescence;HK2 cells were transfected with adenovirus(scramble group and sh-P4HA2 group),and Western Blot and enzyme-linked immunosorbent assay were used to ex-plore the effects of P4HA2 on the NF-κB signaling pathway and downstream inflammatory factors at the cellular level.Results:Compared with the mice in the sham operation group,the expression of P4HA2 in the model group was significantly increased,and it was concentrated in the cytoplasm and nucleus of renal tubular cells.After 50 ng/mL,TGF-β stimulated HK2 cells for 24 hours,the expres-sion level of P4HA2 was significantly increased,and the cell morphology changed from cobblestone to needle-like long spindle.Compared with the scramble group,sh-P4HA2 inhibited the expression of proteins related to the NF-κB signaling pathway,and the levels of downstream inflammatory factors,IL-1β,IL-6,and TNF-α,were also downregulated.Conclusion:P4HA2 may regulate the NF-κB sig-naling pathway,inhibit the inflammatory response,and alleviate the development of renal interstitial fibrosis.