Effect of advanced glycation end products on the expression of hypoxia-inducible factor-1α and vascular endothelial growth factor proteins in RF/6A cells

The aim of this study was to investigate the effect of advanced glycation end products (AGEs) on the expression of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) proteins in RF/6A cells cultured in vitro, and to investigate the association between the expression of HIF-1α and VEGF proteins. RF/6A cells were cultured in vitro and treated with AGEs and non-glycated albumin control at various concentrations (0, 50, 100, 200, 400 and 800 mg/l) for 24 h. The expression of the VEGF protein was detected by ELISA, and western blot analysis was used to determine the levels of HIF-1α protein. The expression of HIF-1α and VEGF proteins was significantly higher in the AGE group compared with the non-glycated control group (all P<0.05). With the increase in concentration of AGEs, the expression levels of HIF-1α and VEGF protein increased and reached a maximum at 200 mg/l AGE, then decreased at 400 and 800 mg/l. However this effect was not observed in the non-glycated control groups. There was a positive correlation between the expression of HIF-1α and VEGF (P<0.05). AGEs induced the expression of HIF-1α and VEGF proteins in RF/6A cells in a concentration-dependent manner. AGEs may upregulate the expression of VEGF protein by increasing the levels of HIF-1α protein, demonstrating the potential role of HIF-1α-targeted therapy in neovascularization.