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Ubiquitin-conjugating enzyme UBE2Q2 participates in HUWE1-mediated protection on renal tubulointerstitial fibrosis

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Author:: No author available

Journal Title:: Acta Physiologica Sinica

Issue:: 1

DOI:: 10.13294/j.aps.2022.0007

Key Word:: UBE2Q2;HUWE1;表皮生长因子受体;泛素化修饰;肾小管间质纤维化

Abstract：泛素-蛋白酶体系统在蛋白质降解时发挥着重要的作用.泛素化过程需要E1泛素激活酶、E2泛素结合酶、E3泛素连接酶协同完成.本研究组前期研究证明E3泛素连接酶HUWE1(HECT,UBA and WWE domain containing 1)可降解表皮生长因子受体(epidermal growth factor receptor,EGFR),抑制肾小管间质纤维化.为了进一步明确HUWE1抑制肾小管间质纤维化的机制,本研究鉴定了参与HUWE1降解EGFR过程的E2泛素结合酶.通过real-time PCR观察可能与HUWE1发生相互作用的候选E2泛素结合酶在肾脏损伤模型中的表达变化.用小鼠单侧输尿管结扎(unilateral ureteral obstruction,UUO)模型的肾组织和转化生长因子-β(transforming growth factor-β,TGF-β)刺激的人肾脏近端小管上皮细胞(HK-2细胞)来检测候选E2泛素结合酶的表达量变化.结果显示,与对照组相比,E2泛素结合酶UBE2Q2在UUO术后小鼠肾脏组织中mRNA与蛋白水平均显著下调,在TGF-β刺激的HK-2细胞中UBE2Q2 mRNA和蛋白表达水平也显著下调,与HUWE1表达变化趋势一致,表明在肾脏损伤时E2泛素结合酶UBE2Q2表达水平与HUWE1具有协同性.免疫共沉淀(co-immunoprecipitation,Co-IP)和细胞免疫荧光染色结果验证了HUWE1与UBE2Q2的相互作用.在HK-2细胞中敲低UBE2Q2后,HUWE1、EGFR与泛素的结合均显著降低.上述结果提示,UBE2Q2可能是与HUWE1相互作用的E2泛素结合酶,参与HUWE1对肾小管间质纤维化的抑制作用.

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