Mesenchymal stem cells (MSCs) have a therapeutic effect on diabetic nephropathy (DN) but the underlying mechanism remains unclear. This study was conducted to investigate whether human umbilical cord-MSCs (hUCMSCs) can induce oxidative damage and apoptosis by activating Nrf2. We used a type 2 diabetic rat model and a high-glucose and fat-stimulated human glomerular mesangial cell (hGMC) model. Western blotting, RT-qPCR, and TUNEL staining were performed on animal tissues and cultured cells. Nuclear expression of Nrf2 was detected in the renal tissue. Furthermore, Nrf2 siRNA was used to examine the effects of hUCMSCs on hGMCs. Finally, the effect of hUCMSCs on the Nrf2 upstream signalling pathway was investigated. After treatment with hUCMSCs, Nrf2 showed increased expression and nuclear translocation. After Nrf2-specific knockout in hGMCs, the protective effect of hUCMSCs on apoptosis induced by high-glucose and fat conditions was reduced. Activation of the PI3K signalling pathway may be helpful for ameliorating DN using hUCMSCs. hUCMSCs attenuated renal oxidative damage and apoptosis in type 2 diabetes mellitus and Nrf2 activation is one of the important mechanisms of this effect. hUCMSCs show potential as drug targets for DN.

中文翻译：

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人脐带间充质干细胞通过激活Nrf2减少糖尿病肾病氧化损伤和细胞凋亡

间充质干细胞（MSCs）对糖尿病肾病（DN）有治疗作用，但其潜在机制尚不清楚。本研究旨在研究人脐带间充质干细胞 (hUCMSCs) 是否可以通过激活 Nrf2 诱导氧化损伤和细胞凋亡。我们使用了 2 型糖尿病大鼠模型和高糖脂肪刺激的人肾小球系膜细胞 (hGMC) 模型。对动物组织和培养细胞进行蛋白质印迹、RT-qPCR 和 TUNEL 染色。在肾组织中检测到 Nrf2 的核表达。此外，Nrf2 siRNA 用于检查 hUCMSCs 对 hGMCs 的影响。最后，研究了 hUCMSCs 对 Nrf2 上游信号通路的影响。用 hUCMSCs 处理后，Nrf2 表现出增加的表达和核易位。在 hGMCs 中 Nrf2 特异性敲除后，hUCMSCs 对高糖和脂肪条件诱导的细胞凋亡的保护作用减弱。PI3K 信号通路的激活可能有助于使用 hUCMSCs 改善 DN。hUCMSCs 减轻 2 型糖尿病肾氧化损伤和细胞凋亡，Nrf2 激活是这种作用的重要机制之一。hUCMSCs 显示出作为 DN 药物靶点的潜力。