VEGF increases BMEC monolayer permeability by affecting occludin expression and tight junction assembly
1 Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66047; and 2 Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045 Tight junctions between brain microvessel endothelial cells (BMECs) maintain the blood-brain barrier. Barrier breakdown is associa...
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Veröffentlicht in: | American journal of physiology. Heart and circulatory physiology 2001-01, Vol.280 (1), p.H434-H440 |
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Sprache: | eng |
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Zusammenfassung: | 1 Department of Pharmaceutical Chemistry, University of
Kansas, Lawrence 66047; and 2 Department of Molecular
Biosciences, University of Kansas, Lawrence, Kansas 66045
Tight junctions between
brain microvessel endothelial cells (BMECs) maintain the
blood-brain barrier. Barrier breakdown is associated with brain tumors
and central nervous system diseases. Tumor cell-secreted vascular
endothelial growth factor (VEGF) increases microvasculature
permeability in vivo and is correlated with the induction of clinically
severe brain tumor edema. Here we investigated the
permeability-increasing effect and tight junction formation of VEGF. By
measuring [ 14 C]sucrose flux and transendothelial
electrical resistance (TER) across BMEC monolayer cultures, we found
that VEGF increased sucrose permeability and decreased TER. 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 BMEC lysates revealed that the level of occludin but not of
ZO-1 was lowered by VEGF treatment. These results suggest that VEGF
increases BMEC monolayer permeability by reducing occludin expression
and disrupting ZO-1 and occludin organization, which leads to tight
junction disassembly. Occludin and ZO-1 appear to be downstream
effectors of the VEGF signaling pathway.
vascular permeability factor; blood-brain barrier; ZO-1; brain
microvessel endothelial cell; vascular endothelial growth factor |
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ISSN: | 0363-6135 1522-1539 |
DOI: | 10.1152/ajpheart.2001.280.1.h434 |