Blockade of VEGF accelerates proteinuria, via decrease in nephrin expression in rat crescentic glomerulonephritis.

Area of Science:

• Nephrology
• Molecular Biology
• Angiogenesis Research

Background:

• Vascular endothelial growth factor (VEGF) is crucial for maintaining kidney vascular networks.
• Soluble fms-like tyrosine kinase 1 (sFlt-1) inhibits VEGF activity by binding circulating VEGF.
• Progressive glomerulonephritis (GN) involves damage to the kidney's filtration barrier and vasculature.

Purpose of the Study:

• To investigate the role of VEGF in maintaining kidney function and structure during progressive glomerulonephritis (GN).
• To determine the effects of VEGF inhibition on glomerular filtration barrier integrity and renal vascularization in a rat model of GN.

Main Methods:

• Rats with anti-glomerular basement membrane antibody-induced GN were treated with sFlt-1 to inhibit VEGF activity.
• VEGF activity was blocked by transfecting rats with plasmid DNA encoding the murine sFlt-1 gene.
• Urinary protein excretion, nephrin expression, macrophage infiltration, crescent formation, glomerulosclerosis, interstitial fibrosis, renal function, and peritubular capillary (PTC) loss were assessed.

Main Results:

• VEGF inhibition with sFlt-1 led to massive proteinuria and decreased nephrin expression in nephritic rats.
• Blockade of VEGF also induced mild proteinuria in normal rats.
• sFlt-1 treatment accelerated glomerulosclerosis, interstitial fibrosis, renal dysfunction, and peritubular capillary (PTC) loss in GN rats, without affecting macrophage infiltration or crescent formation.

Conclusions:

• VEGF plays a vital role in preserving podocyte function and maintaining renal vasculature.
• Inhibition of VEGF exacerbates kidney injury, promoting glomerulosclerosis and fibrosis.
• VEGF is protective against progressive renal insults in the kidney.