Blockade of VEGF accelerates proteinuria, via decrease in nephrin expression in rat crescentic glomerulonephritis.
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.
Hara
A
A
Department of Gastroenterology and Nephrology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
Wada
T
T
Furuichi
K
K
Sakai
N
N
Kawachi
H
H
Shimizu
F
F
Shibuya
M
M
Matsushima
K
K
Yokoyama
H
H
Egashira
K
K
Kaneko
S
S
D000818:Animals; D018450:Disease Progression; D005921:Glomerulonephritis / Q000150:complications* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D011507:Proteinuria / Q000209:etiology*; D051381:Rats; D011921:Rats, Inbred WKY; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000502:physiology*
D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A; C113267:nephrin