Hyperuricemia Induces Wnt5a/Ror2 Gene Expression, Epithelial–Mesenchymal Transition, and Kidney Tubular Injury in Mice

Background: hyperuricemia contributes to kidney injury, characterized by tubular injury with epithelial–mesenchymal transition (emt). wnt5a/ror2 signaling drives emt in many kidney pathologies. this study sought to evaluate the involvement of wnt5a/ror2 in hyperuricemia-induced emt in kidney tubular injury. methods: a hyperuricemia model was performed in male swiss background mice (3 months old, 30–40 g) with daily intraperitoneal injections of 125 mg/kg body weight (bw) of uric acid. the mice were terminated on day 7 (ua7, n=5) and on day 14 (ua14, n=5). allopurinol groups (ual7 and ual14, each n=5) were added with oral 50 mg/kg bw of allopurinol treatment. the serum uric acid level was quantified, and tubular injury was assessed based on pas staining. reverse transcriptase- pcr was done to quantify wnt5a, ror2, e-cadherin, and vimentin expressions. ihc staining was done for e-cadherin and collagen i. we used the shapiro–wilk for normality testing and one-way anova for variance analysis with a p<0.05 as significance level using spss 22 software.results: the hyperuricemia groups had a higher uric acid level, which was associated with a higher tubular injury score. meanwhile, the allopurinol groups had a significantly lower uric acid level and tubular injury than the uric acid groups. reverse transcriptase-pcr revealed downregulation of the e-cadherin expression. while vimentin and collagen i expression are upregulated, which was associated with a higher wnt5a expression. however, the allopurinol groups had reverse results. immunostaining revealed a reduction in e-cadherin staining in the epithelial cells and collagen i positive staining in the epithelial cells and the interstitial areas. conclusion: hyperuricemia induced tubular injury, which might have been mediated by emt through the activation of wnt5a.