Proinflammatory-factors-carrying-microvesicles from monocytes induced by high glucose enhance the activation of HIF/VEGF pathway in human renal mesangial cells.

objectivesRenal 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.

methodsTHP1 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-1α and VEGF in human renal mesangial cells after treatment with THP1-derived microvesicles were examined by western blot.

resultsThe 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-1α and VEGF in HRMC were augmented by microvesicles.

conclusionsOur 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.