Abstract
BackgroundMesenchymal 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.MethodsWe 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.ResultsAfter 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.ConclusionshUCMSCs 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.
Highlights
Mesenchymal stem cells (MSCs) have a therapeutic effect on diabetic nephropathy (DN) but the underlying mechanism remains unclear
After treatment with Human umbilical cord mesenchymal stem cell (hUCMSC), blood glucose levels were significantly decreased in the DM/MSC group (Fig. 2c, P < 0.05)
We found that malondialdehyde levels in the renal tissue were significantly higher in diabetic rats (DM) than in control rats (Ctrl), which was reversed by hUCMSC treatment (DM/ MSC; P < 0.05, Fig. 3a)
Summary
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 cordMSCs (hUCMSCs) can induce oxidative damage and apoptosis by activating Nrf. Mesenchymal stem cells (MSCs) are a type of undifferentiated cells with multi-differentiation potential, self-renewal ability, and Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important transcription factor that regulates oxidative stress, a condition important in the development of diabetes. Nrf regulates oxidative damage in type 2 diabetes mellitus [9, 10], and has an anti-apoptotic effect [11,12,13]. Nrf is activated via the β-catenin signalling pathway and is involved in preventing apoptosis in renal tubular epithelial cells [12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
