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

ABSTRACT

BACKGROUND: Vascular endothelial growth factor (VEGF) is an endothelial cell 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 mRNA 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/Flk-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 studies are needed to study the role of hypoxia and other cytokines in relation to VEGF in this model.