Overexpression of VEGF165b in podocytes reduces glomerular permeability. Academic Article uri icon

Overview

abstract

  • The observation that therapeutic agents targeting vascular endothelial growth factor-A (VEGF-A) associate with renal toxicity suggests that VEGF plays a role in the maintenance of the glomerular filtration barrier. Alternative mRNA splicing produces the VEGF(xxx)b family, which consists of antiangiogenic peptides that reduce permeability and inhibit tumor growth; the contribution of these peptides to normal glomerular function is unknown. Here, we established and characterized heterozygous and homozygous transgenic mice that overexpress VEGF(165)b specifically in podocytes. We confirmed excess production of glomerular VEGF(165)b by reverse transcriptase-PCR, immunohistochemistry, and ELISA in both heterozygous and homozygous animals. Macroscopically, the mice seemed normal up to 18 months of age, unlike the phenotype of transgenic podocyte-specific VEGF(164)-overexpressing mice. Animals overexpressing VEGF(165)b, however, had a significantly reduced normalized glomerular ultrafiltration fraction with accompanying changes in ultrastructure of the glomerular filtration barrier on the vascular side of the glomerular basement membrane. These data highlight the contrasting properties of VEGF splice variants and their impact on glomerular function and phenotype.

publication date

  • August 5, 2010

Research

keywords

  • Kidney Glomerulus
  • Podocytes
  • Vascular Endothelial Growth Factor A

Identity

PubMed Central ID

  • PMC3013528

Scopus Document Identifier

  • 77956533706

Digital Object Identifier (DOI)

  • 10.1681/ASN.2009060617

PubMed ID

  • 20688932

Additional Document Info

volume

  • 21

issue

  • 9