Exosomal lncRNA ZEB1-AS1 secreted from mesenchymal stem cells attenuates diabetic nephropathy by regulating miR-142-5p/PTEN axis
10.3760/cma.j.cn311282-20221210-00686
- VernacularTitle:间充质干细胞外泌体lncRNA ZEB1-AS1通过靶向miR-142-5p/PTEN调控糖尿病性肾病
- Author:
Defeng LIU
1
;
Fanling HU
Author Information
1. 临沂市中心医院肾内科，临沂 276400
- Keywords:
Diabetic nephropathy;
Adipose-derived mesenchymal stem cells exosomes;
LncRNA ZEB1;
Inflammation;
Oxidative stress
- From:
Chinese Journal of Endocrinology and Metabolism
2023;39(8):695-703
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the role of an exosomal long non-coding RNA zinc finger E-box-bingding homeobox 1 antisense 1(ZEB1-AS1) from adipose-derived MSC(adMSC) and its action mechanism in DN.Methods:DN rat model and high glucose(HG)-induced glomerular mesangial cell(GMCs) model treated with exosomal ZEB1-AS1 from adMSC were used for biochemical analysis and inflammation/oxidative stress assessment. The binding relationships among ZEB1-AS1, microRNA(miR)-142-5p, and phosphatase and tensin homolog deleted on chromosome 10(PTEN) were confirmed by dual luciferase reporter assay. Western blotting was used for the measurement of PTEN protein level.Results:adMSC-secreted exosomal ZEB1-AS1 reduced the levels of blood glucose, serum creatinine, 24 h urinary protein, kidney weight, fibrosis, and inflammatory cell infiltrations in DN rats. Meanwhile, both in DN rats and HG-induced GMCs, the levels of tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β were inhibited, but glutathione peroxidase(GPx), superoxide dismutase(SOD), catalase(CAT), and glutathione(GSH) were promoted by exosomal ZEB1-AS1 treatment. Additionally, miR-142-5p was identified to bind to ZEB1-AS1, while miR-142-5p further targeted PTEN. miR-142-5p overexpression or PTEN silencing reversed the inhibiting effects of exosomal ZEB1-AS1 on inflammatory cytokine levels and the promoting effects on the concentrations of antioxidant enzymes.Conclusion:Exosomal ZEB1-AS1 from adMSC prevents DN progression by controlling inflammation and oxidative stress via the miR-142-5p/PTEN pathway, suggesting that ZEB1-AS1 may serve as a potential and effective therapeutic target for treating DN.
