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Fc-saxatilin suppresses hypoxia-induced vascular leakage by regulating endothelial occludin expression
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 권일 | - |
dc.contributor.author | 남효석 | - |
dc.contributor.author | 허지회 | - |
dc.contributor.author | 최현정 | - |
dc.date.accessioned | 2017-11-02T08:37:44Z | - |
dc.date.available | 2017-11-02T08:37:44Z | - |
dc.date.issued | 2017 | - |
dc.identifier.issn | 0340-6245 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/154691 | - |
dc.description.abstract | Vascular 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.statementOfResponsibility | restriction | - |
dc.language | English, French(Summary), German(Summary) | - |
dc.publisher | Schattauer | - |
dc.relation.isPartOf | THROMBOSIS AND HAEMOSTASIS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Brain/blood supply* | - |
dc.subject.MESH | Capillary Permeability/drug effects* | - |
dc.subject.MESH | Cell Hypoxia | - |
dc.subject.MESH | Cell Line | - |
dc.subject.MESH | Disintegrins/pharmacology* | - |
dc.subject.MESH | Dose-Response Relationship, Drug | - |
dc.subject.MESH | Focal Adhesion Kinase 1/metabolism | - |
dc.subject.MESH | Human Umbilical Vein Endothelial Cells/drug effects* | - |
dc.subject.MESH | Human Umbilical Vein Endothelial Cells/metabolism | - |
dc.subject.MESH | Human Umbilical Vein Endothelial Cells/pathology | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Infarction, Middle Cerebral Artery/drug therapy* | - |
dc.subject.MESH | Infarction, Middle Cerebral Artery/metabolism | - |
dc.subject.MESH | Infarction, Middle Cerebral Artery/pathology | - |
dc.subject.MESH | Integrin alphaVbeta3/metabolism | - |
dc.subject.MESH | Ischemic Attack, Transient/drug therapy* | - |
dc.subject.MESH | Ischemic Attack, Transient/metabolism | - |
dc.subject.MESH | Ischemic Attack, Transient/pathology | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Matrix Metalloproteinase 2/metabolism | - |
dc.subject.MESH | Matrix Metalloproteinase 9/metabolism | - |
dc.subject.MESH | Mice | - |
dc.subject.MESH | Mice, Inbred ICR | - |
dc.subject.MESH | Microvessels/drug effects* | - |
dc.subject.MESH | Microvessels/metabolism | - |
dc.subject.MESH | Microvessels/pathology | - |
dc.subject.MESH | Occludin/metabolism* | - |
dc.subject.MESH | Phosphorylation | - |
dc.subject.MESH | Reperfusion Injury/metabolism | - |
dc.subject.MESH | Reperfusion Injury/pathology | - |
dc.subject.MESH | Reperfusion Injury/prevention & control* | - |
dc.subject.MESH | Signal Transduction/drug effects | - |
dc.subject.MESH | Time Factors | - |
dc.title | Fc-saxatilin suppresses hypoxia-induced vascular leakage by regulating endothelial occludin expression | - |
dc.type | Article | - |
dc.publisher.location | Germany | - |
dc.contributor.college | College of Medicine | - |
dc.contributor.department | Dept. of Life Science | - |
dc.contributor.googleauthor | H.-J. Choi | - |
dc.contributor.googleauthor | I. Kwon | - |
dc.contributor.googleauthor | N.-E. Kim | - |
dc.contributor.googleauthor | J. Kim | - |
dc.contributor.googleauthor | S. An | - |
dc.contributor.googleauthor | S. Kang | - |
dc.contributor.googleauthor | S.-Y. Hong | - |
dc.contributor.googleauthor | H. S. Nam | - |
dc.contributor.googleauthor | J. H. Heo | - |
dc.identifier.doi | 10.1160/TH16-06-0469. | - |
dc.contributor.localId | A01273 | - |
dc.contributor.localId | A04369 | - |
dc.contributor.localId | A04211 | - |
dc.contributor.localId | A00245 | - |
dc.relation.journalcode | J02726 | - |
dc.identifier.pmid | 28004056 | - |
dc.identifier.url | https://th.schattauer.de/en/contents/archive/issue/2460/manuscript/27021.html | - |
dc.subject.keyword | Fc-saxatilin | - |
dc.subject.keyword | disintegrin | - |
dc.subject.keyword | endothelial permeability | - |
dc.subject.keyword | occludin | - |
dc.contributor.alternativeName | Kwon, Il | - |
dc.contributor.alternativeName | Nam, Hyo Suk | - |
dc.contributor.alternativeName | Heo, Ji Hoe | - |
dc.contributor.affiliatedAuthor | Nam, Hyo Suk | - |
dc.contributor.affiliatedAuthor | Heo, Ji Hoe | - |
dc.contributor.affiliatedAuthor | Choi, Hyun-Jung | - |
dc.contributor.affiliatedAuthor | Kwon, Il | - |
dc.citation.title | Thrombosis and Haemostasis | - |
dc.citation.volume | 117 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 595 | - |
dc.citation.endPage | 605 | - |
dc.identifier.bibliographicCitation | THROMBOSIS AND HAEMOSTASIS, Vol.117(3) : 595-605, 2017 | - |
dc.date.modified | 2017-11-01 | - |
dc.identifier.rimsid | 44149 | - |
dc.type.rims | ART | - |
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