Objective       To explore the effect of uremic toxin indoxyl sulfate (IS) on inducing renal fibrosis in mice and its underlying mechanism.         Methods       A total of 24 healthy 3-week-old male CD-1 mice (weighting 14~15 g) were used to establish 1/2 nephrectomy model and then randomly divided into IS treatment group (n=12) and blank control group (n=12). The IS treatment group received intraperitoneal injection of IS at dose of 100 mg/(kg·d）

and the control group received the same volume of phosphate buffer saline for 4 weeks. At the end of 4 weeks

the kidney samples were taken

and the mouse renal interstitial collagen deposition was observed by Masson staining. Expression levels of renal α-smooth muscle actin (α-SMA) and β-catenin were detected by immunohistochemical staining

and the changes of β-catenin protein were also detected by Western blotting. Human renal proximal tubular epithelial cells (HK-2 cells) were incubated with different concentrations of IS (0

2

10

and 50 mg/L) for 72 h

and the expression of β-catenin was measured by Western blotting.         Results       Compared with the control group

Masson staining showed that the IS-injected mice had significantly increased collagen deposition (2.43±0.51 vs 6.57±0.51

P0.05)

and the expression levels of β-catenin (0.87±0.74 vs 10.87±1.21

P0.05) and α-SMA (1.30±0.56 vs 13.53±0.50

P0.05) in the proximal and distal tubule epithelial cells of the IS-injected mice were obviously increased. In the HK-2 cells incubated with IS

the protein levels of β-catenin increased significantly (0.71±0.71 vs 0.96±0.70

0.71±0.71 vs 1.10±0.95

P0.01) in a dose-dependent manner.         Conclusion       IS can promote the progress of renal fibrosis in the mice

which may be through activating Wnt/β-catenin signaling pathway.