Abstract: Objective To investigate the effect and mechanism of WISP-1 on renal tubular epithelial cell fibrosis in rats with renal fibrosis. Methods Twenty-four adult rats and renal tubular epithelial cell line(NEK-52E) were selected for in vivo and in vitro experiments. The rats were randomly divided into control group and study group, and the in vivo renal fibrosis model was established. The expression of WISP-1 in the study group was blocked. The cell lines were induced to fibrosis followed by WISP-1 over-expression or inhibition. The related indicators of fibrosis were observed. Results Protein and mRNA level of Collagen Ⅰ(Col Ⅰ), fibronectin (FN), transforming growth factor-β1(TGF-β1) in WISP-1 over-expression group were all higher than those in control group. The protein and mRNA level of Col Ⅰ, FN and TGF-β1 in the WISP-1 inhibition group were lower than those in the control group(P＜0.05). WISP-1 blockade attenuated the pathological changes of renal fibrosis. The protein and mRNA levels of Col Ⅰ, FN, α-smooth muscle actin(α-SMA), TGF-β1, LC3 and Beclin-1 in the study group were lower than those in the control group, and the level of ubiquitin binding protein p62(SQSTM1/p62) was higher than that in the control group(P＜0.05). The expression of LC3 and Beclin-1 in WISP-1 inhibitor group was lower than that in the control group and the expression of SQSTM1/p62 was higher than that in the control group. The expression of LC3 and Beclin-1 in the WISP-1 over-expression group was higher than that in the control group, and the expression of SQSTM1/p62 was lower than that in the control group. Conclusions Overexpression of WISP-1 promotes the fibrosis of rat renal tubular epithelial cells, and enhanced TGF-β1-mediated autophagy might be a underlying mechanism to mediate renal fibrosis.

Key words: WISP-1, chronic kidney disease, renal fibrosis, mechanism of action