Angiopoietin-1 reduces vascular endothelial growth factor-induced brain endothelial permeability via upregulation of ZO-2

Brain microvessels possess barrier structures comprising tight junctions which are critical for the maintenance of central nervous system homeostasis. Brain vascular diseases, such as ischemic stroke damage to blood-brain barrier, increase the vascular permeability, and then lead to vasogenic brain...

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Veröffentlicht in:International journal of molecular medicine 2009-02, Vol.23 (2), p.279-284
Hauptverfasser: Lee, Sae-Won, Kim, Woo, Jun, Hyoung-Oh, Choi, Yoon, Kim, Kyu-Won
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container_issue 2
container_start_page 279
container_title International journal of molecular medicine
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creator Lee, Sae-Won
Kim, Woo
Jun, Hyoung-Oh
Choi, Yoon
Kim, Kyu-Won
description Brain microvessels possess barrier structures comprising tight junctions which are critical for the maintenance of central nervous system homeostasis. Brain vascular diseases, such as ischemic stroke damage to blood-brain barrier, increase the vascular permeability, and then lead to vasogenic brain edema. Herein, we examined whether angiopoietin-1 (Ang-1) could regulate zonula occludens-2 (ZO-2) expression and counteract vascular endothelial growth factor (VEGF)-induced vascular permeability. When we treated brain microvascular endothelial cells with Ang-1, Ang-1 caused a time- and dose-dependent increase of ZO-2 and down-regulation in endothelial permeability. VEGF, one of the key regulators of ischemia-induced vascular permeability, increased endothelial cell permeability in vitro, whereas, Ang-1 reversed this VEGF effect by up-regulating ZO-2 expression. Additionally, the recovery effect of Ang-1 on permeability was strongly blocked by siRNA against ZO-2. Collectively, our results suggest that Ang-1 shows anti-permeability activity through up-regulation of ZO-2.
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source Spandidos Publications Journals; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects Angiopoietin-1 - pharmacology
Blood-Brain Barrier - metabolism
Brain - blood supply
Brain - metabolism
Capillary Permeability
Endothelial Cells - drug effects
Endothelial Cells - metabolism
Endothelium, Vascular - cytology
Endothelium, Vascular - metabolism
Humans
Membrane Proteins - genetics
Membrane Proteins - metabolism
RNA, Small Interfering - genetics
RNA, Small Interfering - metabolism
Up-Regulation
Vascular Endothelial Growth Factor A - metabolism
Zonula Occludens-2 Protein
title Angiopoietin-1 reduces vascular endothelial growth factor-induced brain endothelial permeability via upregulation of ZO-2
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