Expression of vascular endothelial growth factor and its receptors Flt-1 and KDR/Flk-1 in chronic cyclosporine nephrotoxicity

Background. Vascular endothelial growth factor (VEGF) is an endothelial cel l mitogen involved in angiogenesis, wound healing, and inflammation. Methods, Rats placed on low salt diet (LSD) or normal salt diet (NSD) were treated with cyclosporine (CsA) or vehicle (VH) and killed at 7 or 28 days. We studied the expression of VEGF and its receptors Flt-1 and KDR/Flk-1 mR NA by Northern and that of VEGF protein by Western blot. Results. CsA induced VEGF mRNA and protein expressions at 7 and 28 days in LSD rats. At 7 days, CsA up-regulated the expression of Flt-1 and KDR/Flk-1 receptors; however, at 28 days, Flt-1 remained unchanged whereas KDR/Flt-1 expression declined. In NSD rats, in which the lesion did not develop, the expression of VEGF and its receptors remained similar to control. Conclusions. What causes VEGF to be up-regulated remains unclear. Further s tudies are needed to study the role of hypoxia and other cytokines in relat ion to VEGF in this model.