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Fc-saxatilin suppresses hypoxia-induced vascular leakage by regulating endothelial occludin expression

DC FieldValueLanguage
dc.contributor.author권일-
dc.contributor.author남효석-
dc.contributor.author허지회-
dc.contributor.author최현정-
dc.date.accessioned2017-11-02T08:37:44Z-
dc.date.available2017-11-02T08:37:44Z-
dc.date.issued2017-
dc.identifier.issn0340-6245-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/154691-
dc.description.abstractVascular leakage due to compromised integrity of the endothelial barrier is closely associated with brain damage in several neurological disorders, including ischaemic stroke. Saxatilin, a snake venom disintegrin containing the Arg-Gly-Asp (RGD) motif, exerts thrombolytic and antiplatelet effects by interacting with multiple integrins on platelets. Integrin signalling is indispensable for regulation of endothelial permeability. Saxatilin may play a role in vascular leakage after ischaemia because it has high affinity for endothelial integrins. Here, we determined whether Fc-saxatilin, an Fc-fusion protein of saxatilin, could prevent vascular leakage under hypoxic or ischaemic conditions. In mouse brain microvascular endothelial cells, hypoxia increased the permeability to FITC-dextran, and this effect was attenuated by Fc-saxatilin treatment. Fc-saxatilin also blocked vascular leakage of Evans Blue in the ischaemic brain induced by middle cerebral artery occlusion in mice. Furthermore, the expression of occludin, a tight junction protein, was reduced by hypoxia in endothelial cells. This downregulation of occludin was attenuated by Fc-saxatilin treatment. We also determined the activity of matrix metalloproteinases (MMPs) 2 and 9 because they are implicated in the degradation of occludin and of the microvascular basal lamina. Hypoxia increased MMP-9 activity, and this increase was attenuated by Fc-saxatilin treatment. Fc-saxatilin specifically bound to integrin αvβ3 of the endothelial cells and inhibited hypoxia-induced activation of FAK, a downstream signalling molecule in integrin-dependent signal transduction. Taken together, these results provide new insights into the mechanism via which Fc-saxatilin, as an integrin antagonist, prevents vascular leakage under ischemic conditions by regulating occludin expression in endothelial tight junctions.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish, French(Summary), German(Summary)-
dc.publisherSchattauer-
dc.relation.isPartOfThrombosis and Haemostasis-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHBrain/blood supply*-
dc.subject.MESHCapillary Permeability/drug effects*-
dc.subject.MESHCell Hypoxia-
dc.subject.MESHCell Line-
dc.subject.MESHDisintegrins/pharmacology*-
dc.subject.MESHDose-Response Relationship, Drug-
dc.subject.MESHFocal Adhesion Kinase 1/metabolism-
dc.subject.MESHHuman Umbilical Vein Endothelial Cells/drug effects*-
dc.subject.MESHHuman Umbilical Vein Endothelial Cells/metabolism-
dc.subject.MESHHuman Umbilical Vein Endothelial Cells/pathology-
dc.subject.MESHHumans-
dc.subject.MESHInfarction, Middle Cerebral Artery/drug therapy*-
dc.subject.MESHInfarction, Middle Cerebral Artery/metabolism-
dc.subject.MESHInfarction, Middle Cerebral Artery/pathology-
dc.subject.MESHIntegrin alphaVbeta3/metabolism-
dc.subject.MESHIschemic Attack, Transient/drug therapy*-
dc.subject.MESHIschemic Attack, Transient/metabolism-
dc.subject.MESHIschemic Attack, Transient/pathology-
dc.subject.MESHMale-
dc.subject.MESHMatrix Metalloproteinase 2/metabolism-
dc.subject.MESHMatrix Metalloproteinase 9/metabolism-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred ICR-
dc.subject.MESHMicrovessels/drug effects*-
dc.subject.MESHMicrovessels/metabolism-
dc.subject.MESHMicrovessels/pathology-
dc.subject.MESHOccludin/metabolism*-
dc.subject.MESHPhosphorylation-
dc.subject.MESHReperfusion Injury/metabolism-
dc.subject.MESHReperfusion Injury/pathology-
dc.subject.MESHReperfusion Injury/prevention & control*-
dc.subject.MESHSignal Transduction/drug effects-
dc.subject.MESHTime Factors-
dc.titleFc-saxatilin suppresses hypoxia-induced vascular leakage by regulating endothelial occludin expression-
dc.typeArticle-
dc.publisher.locationGermany-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Life Science-
dc.contributor.googleauthorH.-J. Choi-
dc.contributor.googleauthorI. Kwon-
dc.contributor.googleauthorN.-E. Kim-
dc.contributor.googleauthorJ. Kim-
dc.contributor.googleauthorS. An-
dc.contributor.googleauthorS. Kang-
dc.contributor.googleauthorS.-Y. Hong-
dc.contributor.googleauthorH. S. Nam-
dc.contributor.googleauthorJ. H. Heo-
dc.identifier.doi10.1160/TH16-06-0469.-
dc.contributor.localIdA01273-
dc.contributor.localIdA04369-
dc.contributor.localIdA04211-
dc.contributor.localIdA00245-
dc.relation.journalcodeJ02726-
dc.identifier.pmid28004056-
dc.identifier.urlhttps://th.schattauer.de/en/contents/archive/issue/2460/manuscript/27021.html-
dc.subject.keywordFc-saxatilin-
dc.subject.keyworddisintegrin-
dc.subject.keywordendothelial permeability-
dc.subject.keywordoccludin-
dc.contributor.alternativeNameKwon, Il-
dc.contributor.alternativeNameNam, Hyo Suk-
dc.contributor.alternativeNameHeo, Ji Hoe-
dc.contributor.affiliatedAuthorNam, Hyo Suk-
dc.contributor.affiliatedAuthorHeo, Ji Hoe-
dc.contributor.affiliatedAuthorChoi, Hyun-Jung-
dc.contributor.affiliatedAuthorKwon, Il-
dc.citation.titleThrombosis and Haemostasis-
dc.citation.volume117-
dc.citation.number3-
dc.citation.startPage595-
dc.citation.endPage605-
dc.identifier.bibliographicCitationThrombosis and Haemostasis, Vol.117(3) : 595-605, 2017-
dc.date.modified2017-11-01-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers

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