Chen Yin-Yin, Hong Han, Lei Yu-Ting, Zou Jia, Yang Yi-Ya, He Li-Yu
Department of Nephrology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha Clinical Research Center for Kidney Disease, Hunan Clinical Research Center for Chronic Kidney Disease, Changsha, 410000, Hunan Province, P. R. China.
Department of Nephrology, The Second Xiangya Hospital of Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, 410011, Hunan Province, P. R. China.
Cell Death Discov. 2022 Sep 30;8(1):401. doi: 10.1038/s41420-022-01191-2.
Obesity-related glomerulopathy is a secondary glomerular disease and its incidence has been increased globally in parallel with the obesity epidemic. ORG emerged as a growing cause of end-stage renal disease in recent years. Unbalanced production of adipokines at the adipose tissue as well as low-grade inflammatory processes play central roles in ORG progression. ORG mouse model with ACE2-knockout was generated and kidney injury was evaluated by biochemistry and histological staining assays. Protein and mRNA expressions were quantified by ELISA, western blot or qRT-PCR methods. ACE2 deficiency aggravated ORG-related renal injuries and stimulated both lipid accumulation and inflammatory responses. Further, Nrf2 pathway was deactivated upon ACE2-knockout. By contrast, ACE2 overexpression reactivated Nrf2 pathway and ameliorated ORG symptoms by decreasing fat deposition and reducing inflammatory responses. Our data demonstrated that ACE2 exerted the beneficial effects by acting through Nrf2 signaling pathway, suggesting the protective role of ACE2 against lipid accumulation and inflammatory responses in ORG pathogenesis.
肥胖相关肾小球病是一种继发性肾小球疾病，其发病率在全球范围内随着肥胖流行而上升。近年来，肥胖相关肾小球病已成为终末期肾病的一个日益重要的病因。脂肪组织中脂肪因子的产生失衡以及低度炎症过程在肥胖相关肾小球病的进展中起核心作用。构建了ACE2基因敲除的肥胖相关肾小球病小鼠模型，并通过生化和组织学染色分析评估肾损伤。通过ELISA、蛋白质印迹或qRT-PCR方法对蛋白质和mRNA表达进行定量分析。ACE2缺乏加重了肥胖相关肾小球病相关的肾损伤，并刺激了脂质积累和炎症反应。此外，ACE2基因敲除后Nrf2通路失活。相比之下，ACE2过表达可重新激活Nrf2通路，并通过减少脂肪沉积和减轻炎症反应来改善肥胖相关肾小球病症状。我们的数据表明，ACE2通过Nrf2信号通路发挥有益作用，提示ACE2在肥胖相关肾小球病发病机制中对脂质积累和炎症反应具有保护作用。
