Setyaningsih Wiwit Ananda Wahyu, Arfian Nur, Suryadi Efrayim, Romi Muhammad Mansyur, Tranggono Untung, Sari Dwi Cahyani Ratna
Department of Anatomy, Medical Faculty, Universitas Gadjah Mada, Yogyakarta, Indonesia.
Department of Surgery, Medical Faculty, Universitas Gadjah Mada, Yogyakarta, Indonesia.
Iran J Med Sci. 2018 Mar;43(2):164-173.
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.
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.
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.
Hyperuricemia induced tubular injury, which might have been mediated by EMT through the activation of Wnt5a.
高尿酸血症会导致肾损伤，其特征为伴有上皮-间质转化（EMT）的肾小管损伤。Wnt5a/Ror2信号通路在多种肾脏疾病中驱动EMT。本研究旨在评估Wnt5a/Ror2在高尿酸血症诱导的肾小管损伤EMT中的作用。
对雄性瑞士背景小鼠（3月龄，30 - 40克）建立高尿酸血症模型，每日腹腔注射125毫克/千克体重的尿酸。在第7天（UA7，n = 5）和第14天（UA14，n = 5）处死小鼠。别嘌醇组（UAl7和UAl14，每组n = 5）给予口服50毫克/千克体重的别嘌醇治疗。定量血清尿酸水平，并基于PAS染色评估肾小管损伤。进行逆转录聚合酶链反应以定量Wnt5a、Ror2、E-钙黏蛋白和波形蛋白的表达。对E-钙黏蛋白和I型胶原进行免疫组化染色。使用SPSS 22软件进行Shapiro-Wilk正态性检验和单因素方差分析进行方差分析，以P < 0.05作为显著性水平。
高尿酸血症组尿酸水平较高，这与较高的肾小管损伤评分相关。同时，别嘌醇组的尿酸水平和肾小管损伤明显低于尿酸组。逆转录聚合酶链反应显示E-钙黏蛋白表达下调。而波形蛋白和I型胶原表达上调，这与较高的Wnt5a表达相关。然而，别嘌醇组结果相反。免疫染色显示上皮细胞中E-钙黏蛋白染色减少，上皮细胞和间质区域I型胶原阳性染色增加。
高尿酸血症诱导肾小管损伤，这可能是通过Wnt5a激活介导的EMT所致。
