VEGF-induced paracellular permeability in cultured endothelial cells involves urokinase and its receptor.

M. Ali Behzadian, L. Jack Windsor, Nagla Ghaly, Gregory I Liou, Nai Tse Tsai, Ruth B Caldwell

Research output: Contribution to journalArticle

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Abstract

Vascular endothelial growth factor/vascular permeability factor (VEGF) has been implicated in blood/tissue barrier dysfunctions associated with pathological angiogenesis, but the mechanisms of VEGF-induced permeability increase are poorly understood. Here, the role of VEGF-induced extracellular proteolytic activities on the endothelial cell permeability increase is evaluated. Confluent monolayers of bovine retinal microvascular endothelial (BRE) cells grown on porous membrane were treated with VEGF or urokinase plasminogen activator (uPA), and permeability changes were analyzed. uPA-induced permeability was rapid and sustained, but VEGF-induced permeability showed a biphasic pattern: a rapid and transient phase (1-2 h) followed by delayed and sustained phase (6-24 h). The delayed, but not the early phase of VEGF-induced permeability, was blocked by anti-uPA or anti-uPAR (uPA receptor) antibodies and was accompanied by reduced transendothelial electrical resistance, indicating the paracellular route of permeability. Confocal microscopy and Western blotting showed that VEGF treatment increased free cytosolic beta-catenin, which was followed by beta-catenin nuclear translocation, upregulation of uPAR, and downregulation of occludin. Membrane-bound occludin was released immediately after uPA treatment, but with a long delay after VEGF treatment, suggesting a requirement for uPAR gene expression. In conclusion, VEGF induces a sustained paracellular permeability in capillary endothelial cells that is mediated by activation of the uPA/uPAR system.

Original languageEnglish (US)
Pages (from-to)752-754
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume17
Issue number6
StatePublished - Jan 1 2003

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Endothelial cells
Urokinase-Type Plasminogen Activator
Vascular Endothelial Growth Factor A
Cultured Cells
Permeability
Endothelial Cells
Plasminogen Activators
Occludin
beta Catenin
Pathologic Neovascularization
Urokinase Plasminogen Activator Receptors
Membranes
Acoustic impedance
Confocal microscopy
Electric Impedance

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

VEGF-induced paracellular permeability in cultured endothelial cells involves urokinase and its receptor. / Behzadian, M. Ali; Windsor, L. Jack; Ghaly, Nagla; Liou, Gregory I; Tsai, Nai Tse; Caldwell, Ruth B.

In: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 17, No. 6, 01.01.2003, p. 752-754.

Research output: Contribution to journalArticle

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