EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR AND ITS RECEPTORS INRATS WITH PROTEIN-OVERLOAD NEPHROSIS

Background. Based on the fact that vascular endothelial growth factor (VEGF) increases vascular permeability, it is speculated that VEGF mig ht be involved in the development of proteinuria, although this remain s unconfirmed. The production and site of action of VEGF remains uncle ar in nephrotic renal diseases. Methods. Non-radioactive in situ hybri dization was performed to examine the expression of VEGF mRNA and its receptors, flt-1 and KDR/flk-1, in a rat model of nephrosis induced by intraperitoneal injection of bovine serum albumin (BSA). Saline injec ted rats were served as control animals. Results. Neither morphologica l changes nor deposition of immunoglobulin or complement were observed in our model. Proteinuria developed, reaching a maximum level in rats injected with BSA for 3 days, followed by persistent proteinuria unti l day 14. The expression of mRNA for VEGF and the two receptors was ma rkedly upregulated in glomeruli of BSA-induced nephritis compared with the control group. VEGF mRNA was localized in glomerular cells, inclu ding cells in mesangium, visceral and parietal epithelial cells. In co ntrast, flt-1 mRNA and KDR/flk-1 mRNA were expressed on glomerular end othelial cells and cells in mesangium. The ratio of glomerular cells p ositive for VEGF mRNA and its receptors mRNA increased proportionately with the severity of proteinuria. Immunohistochemistry for ED-I and p roliferating cell nuclear antigen showed no significant increase in in filtrating macrophage or cellular proliferation. Conclusions. Our resu lts suggest that altered glomerular expression of VEGF and its recepto rs is not associated with proliferation of endothelial cells, but rath er with proteinuria in BSA-induced nephritis in rats. VEGF may play a different role in different renal diseases.