Autologous transplantation of adipose-derived mesenchymal stem cells ameliorates streptozotocin-induced diabetic nephropathy in rats by inhibiting oxidative stress, pro-inflammatorycytokines and the p38 MAPK signaling pathway

Abstract

Diabetic nephropathy is the leading cause of end-stage renal disease. The aim of this study was to investigate the renoprotective effects of autologous transplantation of adipose-derived mesenchymal stem cells (ADMSCs) and to delineate its underlying mechanisms of action in diabetic nephropathy. Diabetes was induced in adult male Sprague-Dawley rats by streptozotocin (STZ) injection. ADMSCs were administered intravenously 4 weeks after STZ injection and metabolic indices and renal structure were assessed (12 weeks). Markers of diabetes including blood glucose, cholesterol, triglycerides, urea nitrogen and creatinine were measured. Renal pathology, levels of oxidative stress and the expression of pro-inflammatory cytokines and the MAPK signaling pathway members were also determined. Autologous transplantation of ADMSCs significantly attenuated common metabolic disorder symptoms associated with diabetes. Furthermore, ADMSC administration minimized pathological alterations, reduced oxidative damage and suppressed the expression of pro-inflammatory cytokines in the renal tissues of diabetic rats. ADMSC transplantation also decreased the expression of p-p38, p-ERK and p-JNK, which are all important molecules of the MAPK signaling pathway. In conclusion, we provide experimental evidence demonstrating that autologous transplantation of ADMSCs can be used therapeutically to improve metabolic disorder and relieve renal damage induced by diabetes, and that the key mechanisms underlying the positive therapeutic impact of ADMSC treatment in kidneys could be due to the suppression of inflammatory response and oxidative stress.