Vascular endothelial growth factor increases GEnC permeability by affecting the distributions of occludin, ZO-1 and tight juction assembly

Eur Rev Med Pharmacol Sci. 2015;19(14):2621-7.

Abstract

Objective: To explore the molecular mechanism of the increased permeability of glomerular endothelial cells (GEnC) stimulated by vascular endothelial growth factor (VEGF).

Methods: We investigated the permeability-increasing effect and tight junction formation of VEGF by measuring FITC labeled BSA across GEnC monolayer. Then, immunofluorescence and western blot were employed to detect the distributions of occludin and ZO-1.

Results: We found that VEGF increased FITC-BSA permeability. VEGF also caused a loss of occludin and ZO-1 from the endothelial cell junctions, and changed the staining pattern of the cell boundary. Western blot analysis of GEnC lysates revealed that occludin and ZO-1 were redistributed under VEGF treatment.

Conclusions: These results suggested that VEGF could increase GEnC monolayer permeability by changing distributions and organizations of occludin and ZO-1, which lead to tight junction disassembly. Occludin and ZO-1 appeared to be downstream effectors of the VEGF signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Humans
  • Kidney Glomerulus / cytology
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / metabolism*
  • Occludin / metabolism*
  • Permeability / drug effects
  • Rats
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Tight Junctions / drug effects
  • Tight Junctions / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor A / pharmacology
  • Zonula Occludens-1 Protein / metabolism*

Substances

  • OCLN protein, human
  • Occludin
  • Recombinant Proteins
  • TJP1 protein, human
  • Vascular Endothelial Growth Factor A
  • Zonula Occludens-1 Protein
  • vascular endothelial growth factor A, rat