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

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WAHYU SETYANINGSIH WIWIT ANANDA; ARFIAN NUR; SURYADI EFRAYIM; ROMI MUHAMMAD MANSYUR; TRANGGONO UNTUNG; RATNA SARI DWI CAHYANI

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Journal: IRANIAN JOURNAL OF MEDICAL SCIENCES (IJMS) Year:2018 | Volume:43 | Issue:2 Page(s): 164-173

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Title

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

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Keywords

HYPERURICEMIA

TUBULAR INJURY

E-CADHERIN GENE EXPRESSION

VIMENTIN

GENE EXPRESSION

WNT5A/ROR2

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.

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APA: Copy

WAHYU SETYANINGSIH, WIWIT ANANDA, ARFIAN, NUR, SURYADI, EFRAYIM, ROMI, MUHAMMAD MANSYUR, TRANGGONO, UNTUNG, & RATNA SARI, DWI CAHYANI. (2018). HYPERURICEMIA INDUCES WNT5A/ROR2 GENE EXPRESSION, EPITHELIAL–MESENCHYMAL TRANSITION, AND KIDNEY TUBULAR INJURY IN MICE. IRANIAN JOURNAL OF MEDICAL SCIENCES (IJMS), 43(2), 164-173. SID. https://sid.ir/paper/276574/en

Vancouver: Copy

WAHYU SETYANINGSIH WIWIT ANANDA, ARFIAN NUR, SURYADI EFRAYIM, ROMI MUHAMMAD MANSYUR, TRANGGONO UNTUNG, RATNA SARI DWI CAHYANI. HYPERURICEMIA INDUCES WNT5A/ROR2 GENE EXPRESSION, EPITHELIAL–MESENCHYMAL TRANSITION, AND KIDNEY TUBULAR INJURY IN MICE. IRANIAN JOURNAL OF MEDICAL SCIENCES (IJMS)[Internet]. 2018;43(2):164-173. Available from: https://sid.ir/paper/276574/en

IEEE: Copy

WIWIT ANANDA WAHYU SETYANINGSIH, NUR ARFIAN, EFRAYIM SURYADI, MUHAMMAD MANSYUR ROMI, UNTUNG TRANGGONO, and DWI CAHYANI RATNA SARI, “HYPERURICEMIA INDUCES WNT5A/ROR2 GENE EXPRESSION, EPITHELIAL–MESENCHYMAL TRANSITION, AND KIDNEY TUBULAR INJURY IN MICE,” IRANIAN JOURNAL OF MEDICAL SCIENCES (IJMS), vol. 43, no. 2, pp. 164–173, 2018, [Online]. Available: https://sid.ir/paper/276574/en

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