Expression of angiopoietin-1 in hypoxic pericytes: Regulation by hypoxia-inducible factor-2 alpha and participation in endothelial cell migration and tube formation
DC Field | Value | Language |
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dc.contributor.author | Park, Yoon Shin | - |
dc.contributor.author | Kim, Gyungah | - |
dc.contributor.author | Jin, Yoon Mi | - |
dc.contributor.author | Lee, Jee Young | - |
dc.contributor.author | Shin, Jong Wook | - |
dc.contributor.author | Jo, Inho | - |
dc.date.available | 2019-03-08T13:41:04Z | - |
dc.date.issued | 2016-01 | - |
dc.identifier.issn | 0006-291X | - |
dc.identifier.issn | 1090-2104 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/7377 | - |
dc.description.abstract | We previously reported that hypoxia increases angiopoietin-1 (Ang1), but not Ang2, mRNA expression in bovine retinal pericytes (BRP). However, the mechanism underlying Ang1 expression is unknown. Here, we report that Ang1 protein expression increased in hypoxic BRP in a dose- and time-dependent manner. This increase was accompanied by an increase in hypoxia-inducible factor-2 alpha (HIF2 alpha) expression. Transfection with an antisense oligonucleotide for HIF2 alpha partially inhibited the hypoxia-induced increase in Ang1 expression. HIF2 alpha overexpression further potentiated hypoxia-stimulated Ang1 expression, suggesting that HIF2 alpha plays an important role in Ang1 regulation in BRP. When fused the Ang1 promoter (-3040 to +199) with the luciferase reporter gene, we found that hypoxia significantly increased promoter activity by 4.02 +/- 1.68 fold. However, progressive 5'-deletions from 3040 to 1799, which deleted two putative hypoxia response elements (HRE), abolished the hypoxia-induced increase in promoter activity. An electrophoretic mobility shift assay revealed that HIF2 alpha was predominantly bound to a HRE site, located specifically at nucleotides -2715 to -2712. Finally, treatment with conditioned medium obtained from hypoxic pericytes stimulated endothelial cell migration and tube formation, which was completely blocked by co-treatment with anti-Ang1 antibody. This study is the first to demonstrate that hypoxia upregulates Ang1 expression via HIF2 alpha-mediated transcriptional activation in pericytes, which plays a key role in angiogenesis. (C) 2015 Elsevier Inc. All rights reserved. | - |
dc.format.extent | 7 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | ACADEMIC PRESS INC ELSEVIER SCIENCE | - |
dc.title | Expression of angiopoietin-1 in hypoxic pericytes: Regulation by hypoxia-inducible factor-2 alpha and participation in endothelial cell migration and tube formation | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.bbrc.2015.11.108 | - |
dc.identifier.bibliographicCitation | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.469, no.2, pp 263 - 269 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000368652300019 | - |
dc.identifier.scopusid | 2-s2.0-84951010640 | - |
dc.citation.endPage | 269 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 263 | - |
dc.citation.title | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | - |
dc.citation.volume | 469 | - |
dc.type.docType | Article | - |
dc.publisher.location | 미국 | - |
dc.subject.keywordAuthor | Angiogenesis | - |
dc.subject.keywordAuthor | Angiopoietin-1 | - |
dc.subject.keywordAuthor | Hypoxia-inducible factor-2 alpha | - |
dc.subject.keywordAuthor | Hypoxia | - |
dc.subject.keywordAuthor | Pericytes | - |
dc.subject.keywordAuthor | Endothelial cells | - |
dc.subject.keywordPlus | FACTOR (HIF)-1-ALPHA | - |
dc.subject.keywordPlus | FACTOR-I | - |
dc.subject.keywordPlus | HIF-2-ALPHA | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordPlus | TRANSCRIPTION | - |
dc.subject.keywordPlus | HIF-1-ALPHA | - |
dc.subject.keywordPlus | ANGIOGENESIS | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | VARIANT | - |
dc.subject.keywordPlus | SIGNAL | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Biophysics | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Biophysics | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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