Paper Information

Journal:   IRANIAN JOURNAL OF MEDICAL SCIENCES (IJMS)   MARCH 2018 , Volume 43 , Number 2; Page(s) 164 To 173.
 
Paper: 

HYPERURICEMIA INDUCES WNT5A/ROR2 GENE EXPRESSION, EPITHELIAL–MESENCHYMAL TRANSITION, AND KIDNEY TUBULAR INJURY IN MICE

 
 
Author(s):  WAHYU SETYANINGSIH WIWIT ANANDA, ARFIAN NUR*, SURYADI EFRAYIM, ROMI MUHAMMAD MANSYUR, TRANGGONO UNTUNG, RATNA SARI DWI CAHYANI
 
* DEPARTMENT OF ANATOMY FACULTY OF MEDICINE, UNIVERSITAS GADJAH MADA, YOGYAKARTA, PHARMACO STREET, NORTH SEKIP, YOGYAKARTA 55281, INDONESIA
 
Abstract: 

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.

 
Keyword(s): HYPERURICEMIA, TUBULAR INJURY, E-CADHERIN GENE EXPRESSION, VIMENTIN, GENE EXPRESSION, WNT5A/ROR2
 
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