Reactive oxygen species, PKC-1, and PKC- mediate high-glucose-induced vascular endothelial growth factor expression in mesangial cells

mediate high-glucose-induced vascular endothelial growth factor expression in mesangial cells. Am J Physiol Endocrinol Me-tab 293: E1280–E1288, 2007. First published August 21, 2007; doi:10.1152/ajpendo.00223.2007.—Vascular endothelial growth factor (VEGF) is implicated in the development of proteinuria in diabetic nephropathy. High ambient glucose present in diabetes stim-ulates VEGF expression in several cell types, but the molecular mechanisms are incompletely understood. Here primary cultured rat mesangial cells served as a model to investigate the signal transduc-tion pathways involved in high-glucose-induced VEGF expression. Exposure to high glucose (25 mM) significantly increased VEGF mRNA evaluated by real-time PCR by 3 h, VEGF cellular protein content assessed by immunoblotting or immunofluorescence within 24 h, and VEGF secretion by 24 h. High-glucose-induced VEGF expression was blocked by an antioxidant, Tempol, and antisens