E3 ubiquitin ligase gene, WWP2 , is associated with acute kidney injury (AKI ). This research was conducted to explore the role of WWP2 in AKI . AKI cell model was produced in human renal proximal tubular epithelial cell line (HK ‐2) by ischemia‐reperfusion (IR ) injury. CCK8 and flow cytometry assay were performed to explore the influence of WWP2 overexpression on cell proliferation and apoptosis of IR ‐induced HK ‐2 cells. Quantitative real‐time PCR and immunoblotting (IB) were performed to assess the gene and protein expression. Then, the influence of WWP2 on p53 ubiquitylation and degradation was estimated by immunoprecipitation assay. Our data indicated that WWP2 was down‐regulated and p53 was up‐regulated in IR ‐induced HK ‐2 cells. WWP2 overexpression promoted proliferation and inhibited apoptosis of IR ‐induced HK ‐2 cells. And WWP2 interacted with p53 and regulated p53 ubiquitylation and degradation. Furthermore, the influence of WWP2 on cell proliferation and apoptosis was rescued by MG132 (proteasome inhibitor) treatment. In conclusion, our work described for the first time the role of WWP2 in AKI , showing that WWP2 ameliorated AKI by mediating p53 ubiquitylation and degradation. Moreover, the study offers some important insights into the occurrence of AKI and WWP2 may be a novel target of AKI treatment.

中文翻译：

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WWP2通过介导p53泛素化和降解来改善急性肾脏损伤。

E3泛素连接酶基因WWP2与急性肾损伤（AKI）有关。本研究旨在探讨WWP2在AKI中的作用。AKI细胞模型是通过缺血再灌注（IR）损伤在人肾近端肾小管上皮细胞系（HK -2）中产生的。进行了CCK8和流式细胞术测定以探讨WWP2过表达对IR诱导的HK-2细胞增殖和凋亡的影响。进行实时定量PCR和免疫印迹（IB）评估基因和蛋白质表达。然后，通过免疫沉淀测定法估计了WWP2对p53泛素化和降解的影响。我们的数据表明，在IR诱导的HK-2细胞中，WWP2被下调，而p53被上调。WWP2的过表达促进IR诱导的HK-2细胞增殖并抑制其凋亡。WWP2与p53相互作用并调节p53泛素化和降解。此外，通过MG132（蛋白酶体抑制剂）治疗挽救了WWP2对细胞增殖和凋亡的影响。总之，我们的工作首次描述了WWP2在AKI中的作用，表明WWP2通过介导p53泛素化和降解来改善AKI。此外，该研究为AKI的发生提供了一些重要的见识，而WWP2可能是AKI治疗的新靶标。