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 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.
Lee
Sae-Won
SW
Clinical Research Institute, Seoul National University Hospital, Seoul 110-744, Korea. sawolee@snu.ac.kr
Kim
Woo Jean
WJ
Jun
Hyoung-Oh
HO
Choi
Yoon Kyung
YK
Kim
Kyu-Won
KW
D042683:Angiopoietin-1 / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D002199:Capillary Permeability; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D062827:Zonula Occludens-2 Protein
D042683:Angiopoietin-1; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C569046:TJP2 protein, human; D042461:Vascular Endothelial Growth Factor A; D062827:Zonula Occludens-2 Protein