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A Hypoxia-Induced Vascular Endothelial-to-Mesenchymal Transition in Development of Radiation-Induced Pulmonary Fibrosis

DC FieldValueLanguage
dc.contributor.author이창영-
dc.contributor.author조재호-
dc.contributor.author홍진우-
dc.date.accessioned2016-02-04T11:39:36Z-
dc.date.available2016-02-04T11:39:36Z-
dc.date.issued2015-
dc.identifier.issn1078-0432-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/140916-
dc.description.abstractPURPOSE: Radiation-induced pulmonary fibrosis (RIPF) is a late side effect of thoracic radiotherapy. The purpose of our study was to gain further insight into the development of RIPF. EXPERIMENTAL DESIGN/RESULTS: Here, we observed that irradiation of mouse lungs induced collagen deposition, particularly around blood vessels, in the early phase of RIPF. Such deposition subsequently became evident throughout the irradiated tissues. Accompanied by the collagen deposition, vascular EndMT (endothelial-to-mesenchymal transition) began to develop in the early phase of RIPF, before the appearance of EMT (epithelial-to-mesenchymal transition) of alveolar epithelial (AE) II cells in the substantive fibrotic phase. Concomitant with the EndMT, we detected vascular endothelial cell (EC)-specific hypoxic damage in the irradiated lung tissues. In human pulmonary artery endothelial cells (HPAEC), the radiation-induced EndMT via activation of TGFβ-R1/Smad signaling was dependent on HIF1α expression. A novel HIF1α inhibitor, 2-methoxyestradiol (2-ME), inhibited the irradiation-induced EndMT via downregulation of HIF1α-dependent Smad signaling. In vivo, 2-ME inhibited the vascular EndMT, and decreased the collagen deposition associated with RIPF. Furthermore, HIF1α-related EndMT was observed also in human RIPF tissues. CONCLUSIONS: We provide the first evidence that an EndMT occurs in RIPF development and that the EndMT may be effectively inhibited by modulating vascular EC-specific hypoxic damage.-
dc.description.statementOfResponsibilityopen-
dc.format.extent3716~3726-
dc.relation.isPartOfClinical Cancer Research-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleA Hypoxia-Induced Vascular Endothelial-to-Mesenchymal Transition in Development of Radiation-Induced Pulmonary Fibrosis-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentYonsei Biomedical Research Center (연세의생명연구원)-
dc.contributor.googleauthorSeo-Hyun Choi-
dc.contributor.googleauthorZhen-Yu Hong-
dc.contributor.googleauthorJae-Kyung Nam-
dc.contributor.googleauthorHae-June Lee-
dc.contributor.googleauthorJunho Jang-
dc.contributor.googleauthorRan Ji Yoo-
dc.contributor.googleauthorYong Jin Lee-
dc.contributor.googleauthorChang Young Lee-
dc.contributor.googleauthorKyung Hwan Kim-
dc.contributor.googleauthorSeungwoo Park-
dc.contributor.googleauthorYoung Hoon Ji-
dc.contributor.googleauthorYun-Sil Lee-
dc.contributor.googleauthorJaeho Cho-
dc.contributor.googleauthorYoon-Jin Lee-
dc.identifier.doi10.1158/1078-0432.CCR-14-3193-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA03901-
dc.contributor.localIdA04443-
dc.contributor.localIdA03245-
dc.relation.journalcodeJ00564-
dc.identifier.urlhttp://clincancerres.aacrjournals.org/content/21/16/3716.long-
dc.contributor.alternativeNameLee, Chang Young-
dc.contributor.alternativeNameCho, Jae Ho-
dc.contributor.alternativeNameHong, Zhen Yu-
dc.contributor.affiliatedAuthorCho, Jae Ho-
dc.contributor.affiliatedAuthorHong, Zhen-Yu-
dc.contributor.affiliatedAuthorLee, Chang Young-
dc.rights.accessRightsnot free-
dc.citation.volume21-
dc.citation.number16-
dc.citation.startPage3716-
dc.citation.endPage3726-
dc.identifier.bibliographicCitationClinical Cancer Research, Vol.21(16) : 3716-3726, 2015-
Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiation Oncology (방사선종양학교실) > 1. Journal Papers

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