Vascular endothelial growth factor is a survival factor for renal tubular epithelial cells

Vascular endothelial growth factor (VEGF) acts primarily as an endothelial cell mitogen via the "endothelial cell-specific" receptors VEGFR-1 (flt-1) and VEGFR-2 (flk-1/KDR). Only a few nonendothelial cells have been shown to possess functional VEGF receptors. We therefore examined the rat renal tubular epithelial cell line NRK52-E. NRK52-E expressed VEGFR-1 and VEGFR-2 mRNA and protein by RT-PCR, Northern blotting, Western blotting, immunofluorescence, and ligand binding. Serum-starved NRK52-E incubated with VEGF showed a significant increase in [(3)H]thymidine incorporation compared with control (2.3-fold at 1-10 ng/ml, P < 0.05; 3.3-fold at 50-100 ng/ml, P < 0.01). VEGF also protected NRK52-E from hydrogen peroxide-induced apoptosis and necrosis compared with control (annexin-V-FITC-positive cells, 39 vs. 54%; viable cells, 50.5 vs. 39.7%). Immunohistochemical staining using a variety of antibodies showed expression of both VEGF receptors in normal rat renal tubules in vivo. Because VEGF induced a proliferative and an antiapoptotic response in renal tubular epithelial cells, these data suggest that VEGF may act as a survival factor for renal tubular epithelium in vivo.