National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China; Department of Nephrology, The Second Hospital of Jilin University, Nanguan District, Changchun 130041, Jilin, China.
National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
Biomed Pharmacother. 2023 Nov;167:115617. doi: 10.1016/j.biopha.2023.115617. Epub 2023 Oct 4.
Podocyte injury is the common initiating event in focal segmental glomerulosclerosis (FSGS). Oxidative stress and inflammation mediate podocyte injury in FSGS. NRF2 pathway regulates the constitutive and inducible transcription of various genes that encode antioxidant proteins and anti-inflammatory proteins and have pivotal roles in the defense against cellular oxidative stress. In this study, we used adriamycin-induced nephropathy (ADR) in mice as a model of FSGS to confirm that CDDO-Me treatment ameliorated adriamycin-induced kidney damage by improving renal function and kidney histology. CDDO-Me inhibited the level of oxidative stress, inflammation, and apoptosis in adriamycin-induced podocyte injury by activating NRF2 pathway in vivo and in vitro. Furthermore, CDDO-Me stabled the cytoskeleton by regulating NRF2/srGAP2a pathway. Together, these findings show that by activating NRF2 pathway, CDDO-Me could be a therapeutic strategy to prevent the adverse effects of adriamycin-induced podocyte injury.
足细胞损伤是局灶节段性肾小球硬化症（FSGS）的常见起始事件。氧化应激和炎症介导 FSGS 中的足细胞损伤。NRF2 通路调节各种基因的组成型和诱导型转录，这些基因编码抗氧化蛋白和抗炎蛋白，在抵御细胞氧化应激方面发挥着关键作用。在这项研究中，我们使用阿霉素诱导的肾病（ADR）在小鼠中作为 FSGS 的模型，证实 CDDO-Me 通过改善肾功能和肾脏组织学来改善阿霉素诱导的肾脏损伤。CDDO-Me 通过在体内和体外激活 NRF2 通路来抑制氧化应激、炎症和细胞凋亡水平，从而抑制阿霉素诱导的足细胞损伤。此外，CDDO-Me 通过调节 NRF2/srGAP2a 通路稳定细胞骨架。总之，这些发现表明，通过激活 NRF2 通路，CDDO-Me 可能是一种预防阿霉素诱导的足细胞损伤不良影响的治疗策略。
