Mesenchymal stem cells transplantation ameliorates glomerular injury in streptozotocin-induced diabetic nephropathy in rats via inhibiting macrophage infiltration

Abstract

Mesenchymal stem cells (MSCs) treatment has been shown to be effective in diabetic nephropathy (DN). However, the mechanisms involved in the renoprotective effects of MSCs have not been clearly demonstrated. Especially, there was no study on the relationship of MSCs and macrophages in diabetic kidney. To explore the effect of MSCs on macrophages in DN, streptozotocin-induced diabetes animals received no treatment or treatment with MSCs (2×10(6), via tail vein) for two continuous weeks. Eight weeks after treatment, physical, biochemical and morphological parameters were measured. Immunohistochemistry for fibronectin (FN), CollagenI, ED-1, monocyte chemoattractant protein-1 (MCP-1) was performed. Expressions of pro-inflammatory cytokines and hepatocyte growth factor (HGF) at gene level and protein level were determined by real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Blood glucose, urinary albumin excretion, creatinine clearance were significantly reduced after MSCs treatment. The glomerulosclerosis as revealed by periodic acid Schiff stain and expression of FN and CollagenI was also dramatically attenuated. Most importantly, the expression of MCP-1 and the number of infiltrated macrophages in kidney were effectively suppressed by MSCs treatment. The expression of HGF in MSCs group was up-regulated. Meanwhile, the expressions of IL-1β, IL-6 and TNFα were significantly down-regulated by MSCs treatment. Our study suggest that MSCs treatment ameliorates DN via inhibition of MCP-1 expression by secreting HGF, thus reducing macrophages infiltration, down-regulating IL-1β, IL-6, TNFα expression in renal tissue in diabetic rats.