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Isorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice

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dc.contributor.author김태임-
dc.contributor.author전익현-
dc.date.accessioned2021-05-26T17:02:39Z-
dc.date.available2021-05-26T17:02:39Z-
dc.date.issued2021-04-
dc.identifier.issn1661-6596-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/182965-
dc.description.abstractDry eye disease is one of the most common diseases, with increasing prevalence in many countries, but treatment options are limited. Cystic fibrosis transmembrane conductance regulator (CFTR) is a major ion channel that facilitates fluid secretion in ocular surface epithelium and is a potential target of therapeutic agent for the treatment of dry eye disease. In this study, we performed a cell-based, high-throughput screening for the identification of novel natural products that activate CFTR and restore the aqueous deficiency in dry eye. Screening of 1000 natural products revealed isorhamnetin, a flavonol aglycone, as a novel CFTR activator. Electrophysiological studies showed that isorhamnetin significantly increased CFTR chloride current, both wild type and ∆F508-CFTR. Isorhamnetin did not alter intracellular cAMP levels and the activity of other ion channels, including ANO1, ENaC, and hERG. Notably, application of isorhamnetin on mouse ocular surface induced CFTR activation and increased tear volume. In addition, isorhamnetin significantly reduced ocular surface damage and expression of interleukin (IL)-1β, IL-8, and tumor necrosis factor (TNF)-α in an experimental mouse model of dry eye. These data suggest that isorhamnetin may be used to treat dry eye disease.-
dc.description.statementOfResponsibilityopen-
dc.languageINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES-
dc.publisherINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES-
dc.relation.isPartOfINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHAnimals-
dc.subject.MESHCystic Fibrosis Transmembrane Conductance Regulator / genetics*-
dc.subject.MESHDisease Models, Animal-
dc.subject.MESHDry Eye Syndromes / drug therapy*-
dc.subject.MESHDry Eye Syndromes / genetics-
dc.subject.MESHDry Eye Syndromes / pathology-
dc.subject.MESHEpithelial Cells / drug effects-
dc.subject.MESHGene Expression Regulation / drug effects-
dc.subject.MESHHumans-
dc.subject.MESHInterleukin-1beta / genetics-
dc.subject.MESHInterleukin-8 / genetics-
dc.subject.MESHMice-
dc.subject.MESHQuercetin / analogs & derivatives*-
dc.subject.MESHQuercetin / pharmacology-
dc.subject.MESHTumor Necrosis Factor-alpha / genetics-
dc.titleIsorhamnetin Ameliorates Dry Eye Disease via CFTR Activation in Mice-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Ophthalmology (안과학교실)-
dc.contributor.googleauthorHo K Lee-
dc.contributor.googleauthorJinhong Park-
dc.contributor.googleauthorBo-Rahm Kim-
dc.contributor.googleauthorIkhyun Jun-
dc.contributor.googleauthorTae-Im Kim-
dc.contributor.googleauthorWan Namkung-
dc.identifier.doi10.3390/ijms22083954-
dc.contributor.localIdA01080-
dc.contributor.localIdA03541-
dc.relation.journalcodeJ01133-
dc.identifier.eissn1422-0067-
dc.identifier.pmid33921231-
dc.subject.keywordcystic fibrosis transmembrane conductance regulator-
dc.subject.keyworddry eye-
dc.subject.keywordisorhamnetin-
dc.contributor.alternativeNameKim, Tae Im-
dc.contributor.affiliatedAuthor김태임-
dc.contributor.affiliatedAuthor전익현-
dc.citation.volume22-
dc.citation.number8-
dc.citation.startPage3954-
dc.identifier.bibliographicCitationINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.22(8) : 3954, 2021-04-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers

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