J. Kanellis et al., Vascular endothelial growth factor is a survival factor for renal tubular epithelial cells, AM J P-REN, 278(6), 2000, pp. F905-F915
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 tub
ular epithelial cell line NRK52-E. NRK52-E expressed VEGFR-1 and VEGFR-2 mR
NA and protein by RT-PCR, Northern blotting, Western blotting, immunofluore
scence, and ligand binding. Serum-starved NRK52-E incubated with VEGF showe
d a significant increase in [H-3]thymidine incorporation compared with cont
rol (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 n
ecrosis compared with control (annexin-V-FITC-positive cells, 39 vs. 54%; v
iable 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 ma
y act as a survival factor for renal tubular epithelium in vivo.