RECEPTORS OF VASCULAR ENDOTHELIAL GROWTH-FACTOR VASCULAR-PERMEABILITYFACTOR (VEGF VPF) IN FETAL AND ADULT HUMAN KIDNEY - LOCALIZATION AND [I-125] VEGF BINDING-SITES/

Vascular endothelial growth factor (VEGF) has an important function in renal vascular ontogenesis and is constitutively expressed in podocyt es of the adult kidney. The ability of VEGF to be chemotactic for mono cytes and to Increase the activity of collagenase and plasminogen acti vator may have implications for renal development and renal disease. I n humans, the cellular actions of VEGF depend on binding to two specif ic receptors: Flt-1 and KDR. The aims of this study were: (1) to local ize VEGF receptor proteins in human renal ontogenesis; (2) to quantify VEGF binding in human fetal and adult kidney; and (3) to dissect the binding into its two known components: the KDR and Flt-1 receptors. Th e latter aim was achieved by competitive binding of VEGF and placenta growth factor-2, which only binds to Flt-1. Quantification of I-125-VE GF binding sites was performed by autoradiography and computerized den sitometry. By double-label immunohistochemistry, VEGF receptor protein s were localized solely to endothelial cells of preglomerular vessels, glomeruli, and post-glomerular vessels. In developing glomeruli, VEGF receptor protein appeared as soon as endothelial cells were positive for von Willebrand factor. Specific I-125-VEGF binding could be locali zed to renal arteries and veins, glomeruli, and the tubulointerstitial capillary network in different developmental stages, Affinity (K-d) o f adult (aK) and fetal (fK) kidneys was: K-d: glomeruli 38.6 +/- 11.2 (aK, n = 5), 36.3 +/- 7.1 (fK, n = 5); cortical tubulointerstitium 19. 4 +/- 2.6 (aK, n = 5), 11.6 +/- 7.0 (fK, n = 5) pmol. Placenta growth factor-2 displaced VEGF binding in all renal structures by approximate ly 60%. VEGF receptor proteins thus were found only in renal endotheli al cells. A coexpression of both VEGF binding sites could be shown, wi th Flt-1 demonstrating the most abundant VEGF receptor binding sites i n the kidney. These studies support the hypothesis of a function for V EGF in adult kidney that is independent of angiogenesis.