Open AccessHuman umbilical cord mesenchymal stem cells reduce oxidative damage and apoptosis in diabetic nephropathy by activating Nrf2
Author(s) -
Ping Nie,
Xue Bai,
Yan Lou,
Yuexin Zhu,
Shan Jiang,
Lina Zhang,
Na Tian,
Ping Luo,
Bing Li
Publication year - 2021
Publication title -
stem cell research and therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.599
H-Index - 76
ISSN - 1757-6512
DOI - 10.1186/s13287-021-02447-x
Subject(s) - mesenchymal stem cell , apoptosis , diabetic nephropathy , tunel assay , umbilical cord , oxidative stress , stem cell , pi3k/akt/mtor pathway , microbiology and biotechnology , pharmacology , diabetes mellitus , cancer research , chemistry , biology , immunology , endocrinology , biochemistry
Background 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. Methods 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. Results 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. Conclusions 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. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-021-02447-x.