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Articles in PresS, published online ahead of print December 19, 2001
Am J Physiol Cell Physiol, 10.1152/ajpcell.00292.2001
Submitted on June 28, 2001
Accepted on December 8, 2001
1 Medicine, SUNY, Stony Brook, NY, USA
2 Cell Biology, Free University of Brussels, Brussels, Belgium
3 Medicine, Tel Aviv University, Tel Aviv, Israel
4 Medicine, University of Tokyo, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: mgoligorsky{at}mail.som.sunysb.edu.
Glomerular epithelial cells (GEC) are a known site of VEGF production. To investigate the potential effect of VEGF on endothelial cell permeability, immortalized rat GEC were established. Immunocytochemistry of GEC showed VEGF staining. The isoforms of VEGF expressed by GEC were defined by RT-PCR as 121, 165, 185 and 205aa forms. VEGF produced a ca. 2-fold increase in the density of TEM-detectable caveolae in endothelial cells. The electrical resistance of endothelial cells, an indicator of the permeability of monolayers to solutes, was significantly increased by the treatment with the neutralizing antibodies to VEGF and decreased by VEGF, further suggesting that VEGF produces a constitutive increase in endothelial permeability. Transfection of endothelial cells with GFP-caveolin construct showed that VEGF results in a rapid elongation of vesiculo-vacuolar structures decorated with caveolin. In conclusion, cultured GEC retain the ability to synthesize a non-secretory isoform of VEGF. Matrix deposition of VEGF leads to the enhancement of plasmalemmal caveolae expression, elongation of vesiculo-vacuolar structures, and increase in endothelial permeability to solutes.
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