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Local Stabilization of Hypoxia-Inducible Factor-1α Controls Intestinal Inflammation via Enhanced Gut Barrier Function and Immune Regulation

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dc.contributor.author천재희-
dc.date.accessioned2022-09-14T01:11:04Z-
dc.date.available2022-09-14T01:11:04Z-
dc.date.issued2021-01-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/190327-
dc.description.abstractIntestinal epithelial cells are adapted in mucosal hypoxia and hypoxia-inducible factors in these cells can fortify barrier integrity to support mucosal tissue healing. Here we investigated whether hypoxia-related pathways could be proposed as potential therapeutic targets for inflammatory bowel disease. We developed a novel hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, CG-598 which stabilized HIF-1α in the gut tissue. Treatment of CG-598 did not affect extra-intestinal organs or cause any significant adverse effects such as erythropoiesis. In the experimental murine colitis model, CG-598 ameliorated intestinal inflammation with reduction of inflammatory lesions and pro-inflammatory cytokines. CG-598 treatment fortified barrier function by increasing the expression of intestinal trefoil factor, CD73, E-cadherin and mucin. Also, IL-10 and IL-22 were induced from lamina propria CD4+ T-cells. The effectiveness of CG-598 was comparable to other immunosuppressive therapeutics such as TNF-blockers or JAK inhibitors. These results suggest that CG-598 could be a promising therapeutic candidate to treat inflammatory bowel disease.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherFrontiers Research Foundation-
dc.relation.isPartOfFRONTIERS IN IMMUNOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAnimals-
dc.subject.MESHCaco-2 Cells-
dc.subject.MESHCell Line, Tumor-
dc.subject.MESHColitis / drug therapy-
dc.subject.MESHColitis / immunology-
dc.subject.MESHColitis / metabolism-
dc.subject.MESHCytokines / immunology-
dc.subject.MESHCytokines / metabolism-
dc.subject.MESHDisease Models, Animal-
dc.subject.MESHFemale-
dc.subject.MESHHCT116 Cells-
dc.subject.MESHHeLa Cells-
dc.subject.MESHHumans-
dc.subject.MESHHypoxia / drug therapy-
dc.subject.MESHHypoxia / immunology-
dc.subject.MESHHypoxia / metabolism-
dc.subject.MESHHypoxia-Inducible Factor 1, alpha Subunit / immunology*-
dc.subject.MESHHypoxia-Inducible Factor 1, alpha Subunit / metabolism*-
dc.subject.MESHInflammation / immunology*-
dc.subject.MESHInflammation / metabolism*-
dc.subject.MESHInflammatory Bowel Diseases / drug therapy-
dc.subject.MESHInflammatory Bowel Diseases / immunology-
dc.subject.MESHInflammatory Bowel Diseases / metabolism-
dc.subject.MESHIntestinal Mucosa / drug effects-
dc.subject.MESHIntestinal Mucosa / immunology*-
dc.subject.MESHIntestinal Mucosa / metabolism*-
dc.subject.MESHMale-
dc.subject.MESHMice-
dc.subject.MESHMice, Inbred C57BL-
dc.subject.MESHMice, Inbred ICR-
dc.subject.MESHProlyl-Hydroxylase Inhibitors / pharmacology-
dc.subject.MESHTrefoil Factor-3 / immunology-
dc.subject.MESHTrefoil Factor-3 / metabolism-
dc.titleLocal Stabilization of Hypoxia-Inducible Factor-1α Controls Intestinal Inflammation via Enhanced Gut Barrier Function and Immune Regulation-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorYoung-In Kim-
dc.contributor.googleauthorEun-Je Yi-
dc.contributor.googleauthorYoung-Dae Kim-
dc.contributor.googleauthorA Reum Lee-
dc.contributor.googleauthorJiwoung Chung-
dc.contributor.googleauthorHae Chan Ha-
dc.contributor.googleauthorJoong Myung Cho-
dc.contributor.googleauthorSeong-Ryeol Kim-
dc.contributor.googleauthorHyun-Jeong Ko-
dc.contributor.googleauthorJae-Hee Cheon-
dc.contributor.googleauthorYong Rae Hong-
dc.contributor.googleauthorSun-Young Chang-
dc.identifier.doi10.3389/fimmu.2020.609689-
dc.contributor.localIdA04030-
dc.relation.journalcodeJ03075-
dc.identifier.eissn1664-3224-
dc.identifier.pmid33519819-
dc.subject.keywordgut barrier-
dc.subject.keywordhypoxia-inducible factor-
dc.subject.keywordimmune regulation-
dc.subject.keywordinflammatory bowel disease-
dc.subject.keywordprolyl hydroxylase inhibitor-
dc.contributor.alternativeNameCheon, Jae Hee-
dc.contributor.affiliatedAuthor천재희-
dc.citation.volume11-
dc.citation.startPage609689-
dc.identifier.bibliographicCitationFRONTIERS IN IMMUNOLOGY, Vol.11 : 609689, 2021-01-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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