Abstract:Objective To explore the role and mechanism of secreted frizzled related protein 5(SFRP5) in epithelial to mesenchymal transition(EMT) of renal tubular epithelial cells. Methods The humam proximal renal tubular epithelial cell line HK-2 cells were stimulated by transforming growth factor (TGF)-β1 in vitro and incubated with or without SFRP5. The mRNA and protein expression of EMT indexes including E-cadherin and α-SMA were detected by quantitative real-time PCR and Western Blot. The protein levels of fibrosis indexes ［Fibronectin(Fn) and Collagen I(Col-I)］ were also evaluated. The level of phosphorylated β-catenin in cytoplasm or activated β-catenin in nucleus of Wnt/β-catenin signaling pathway was detected by WB. The TOP/FOP-flash luciferase assay was used to evaluate β-catenin-mediated transcription, in addition, the mRNA levels of downstream target genes c-Myc and cyclin D1 were measured. Results The original E-cadherin level of renal epithelial cells decreased, while α-SMA, Fn and Col-I increased after TGF-β1 stimulation. The cytoplasmic level of phosphorylation(site p-S37) of β-catenin decreased and nuclear level of β-catenin increased (P＜0.05). The TOP/FOP ratio was up-regulated, and the transcription of the target genes c-Myc and cyclin D1 increased (P＜0.05). After adding SFRP5 to treat cells, the changes of EMT and fibrosis indexes were reversed, and the above-mentioned markers in abnormally activated Wnt/β-catenin pathway were inhibited, and the inhibiting and protecting effects of SFRP5 were cancelled by SFRP5 specific neutralizing antibody (P＜0.05). Conclusion In this study, it has been found for the first time that SFRP5 can ameliorate the EMT and fibrosis in renal tubular epithelial cells induced by TGF-β1. The mechanism is related to the inhibition of abnormally activated Wnt/β-catenin signaling pathway, which may become a new target for clinical diagnosis and treatment and delaying the progress of chronic kidney disease.