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Iranian Journal of Medical Sciences، جلد ۴۳، شماره ۲، صفحات ۱۶۴-۱۷۳

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عنوان انگلیسی Hyperuricemia Induces Wnt5a/Ror2 Gene Expression, Epithelial–Mesenchymal Transition, and Kidney Tubular Injury in Mice
چکیده انگلیسی مقاله 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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نویسندگان مقاله Wiwit Ananda Wahyu Setyaningsih |
Department of Anatomy Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia

Nur Arfian |


Efrayim Suryadi |


Muhammad Mansyur Romi |


Untung Tranggono |


Dwi Cahyani Ratna Sari |



نشانی اینترنتی http://ijms.sums.ac.ir/article_40525_6d96ac3f398b941dd16064315fdef106.pdf
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