Proinflammatory-Factors-Carrying-Microvesicles From Monocytes Induced By High Glucose Enhance The Activation Of Hif/Vegf Pathway In Human Renal Mesangial Cells

Objectives: Renal mesangial expansion has been identified as a major factor contributing to glomerulosclerosis, a typical symptom of diabetic nephropathy. It is unclear whether microvesicles, known as a mediator for cross-talk between cells and organs, are involved in a profibrotic process. In this study, we are the first to investigate the effect of monocyte-derived microvesicles induced by high glucose on renal mesangial cells. Methods: THP1 cells were evoked by high glucose to generate microvesicles, quantified by ELISA. Glucose uptake by THP1 cells was measured using fluorescently-labeled deoxyglucose analog 2-NBDG as a probe. The contents of inflammatory cytokines in microvesicles were detected by western blot. The expressions of HIF-1 alpha and VEGF in human renal mesangial cells after treatment with THP1-derived microvesicles were examined by western blot. Results: The glucose uptake by THP1 cells was significantly increased after high glucose treatment. High glucose significantly evoked MV generation, which contained increased protein level of IL-6, 8 and MCP-1. The expressions of HIF-1 alpha and VEGF in HRMC were augmented by microvesicles. Conclusions: Our study indicates that monocyte-derived MVs induced by high glucose can carry proinflammatory factors, and enhance the expression of the HIF/VEGF pathway in human renal mesangial cells. Our findings may provide a novel potential mechanism in the progression of diabetic nephropathy.