Vascular endothelial growth factor (
VEGF) is a potent
angiogenic factor that maintains the glomerular and peritubular capillary (PTC) network in the kidney. The soluble form of the
VEGF receptor-1 (soluble
fms-like tyrosine kinase 1 (sFlt-1)) is known to regulate
VEGF activity by binding
VEGF in the circulation. We hypothesized that
VEGF may be beneficial for maintaining glomerular filtration barrier and vascular network in rats with progressive
glomerulonephritis (GN). For blockade of
VEGF activity in vivo, rats were transfected twice with plasmid
DNA encoding the murine sFlt-1 gene into femoral muscle 3 days before and 2 weeks after the induction of
antiglomerular basement membrane antibody-induced GN. Inhibition of
VEGF with sFlt-1 resulted in massive urinary
protein excretion, concomitantly with downregulated expression of
nephrin in nephritic rats. Further, blockade of
VEGF induced mild
proteinuria in normal rats. Administration of sFlt-1 affected neither the infiltration of macrophages nor crescentic formation. In contrast, treatment of sFlt-1 accelerated the progression of glomerulosclerosis and interstitial
fibrosis accompanied with renal dysfunction and PTC loss at day 56.
VEGF may play a role in maintaining the podocyte function as well as renal vasculature, thereby protecting glomeruli and interstitium from progressive renal insults.