Department of Cardiovascular Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Cell Biochem Funct. 2020 Aug;38(6):695-701. doi: 10.1002/cbf.3533. Epub 2020 Apr 5.
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. SIGNIFICANCE OF THE STUDY: Our data elaborates that WWP2 has protective effect against AKI by mediating p53 ubiquitylation and degradation. Thus, WWP2 might be a therapeutic target for AKI.
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。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 AKI 细胞模型。通过 CCK8 和流式细胞术检测过表达 WWP2 对 IR 诱导的 HK-2 细胞增殖和凋亡的影响。通过定量实时 PCR 和免疫印迹 (IB) 评估基因和蛋白表达。然后，通过免疫沉淀测定估计 WWP2 对 p53 泛素化和降解的影响。我们的数据表明，IR 诱导的 HK-2 细胞中 WWP2 下调，p53 上调。过表达 WWP2 促进了 IR 诱导的 HK-2 细胞的增殖并抑制了其凋亡。并且 WWP2 与 p53 相互作用并调节 p53 泛素化和降解。此外，MG132（蛋白酶体抑制剂）处理可挽救 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 泛素化和降解改善 AKI。此外，该研究为 AKI 的发生提供了一些重要的见解，并且 WWP2 可能是 AKI 治疗的新靶标。
我们的数据阐述了 WWP2 通过介导 p53 泛素化和降解对 AKI 具有保护作用。因此，WWP2 可能是 AKI 的治疗靶点。
