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Punicalagin Ameliorates Lupus Nephritis via Inhibition of PAR2

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dc.contributor.author박용범-
dc.contributor.author이상원-
dc.contributor.author문진희-
dc.date.accessioned2020-09-29T04:54:19Z-
dc.date.available2020-09-29T04:54:19Z-
dc.date.issued2020-07-
dc.identifier.issn1661-6596-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/179533-
dc.description.abstractLupus nephritis (LN) is the most frequent phenotype in patients with systemic lupus erythematosus (SLE) and has a high rate of progression to end-stage renal disease, in spite of intensive treatment and maintenance therapies. Recent evidence suggests that protease-activated receptor-2 (PAR2) is a therapeutic target for glomerulonephritis. In this study, we performed a cell-based high-throughput screening and identified a novel potent PAR2 antagonist, punicalagin (PCG, a major polyphenol enriched in pomegranate), and evaluated the effects of PCG on LN. The effect of PCG on PAR2 inhibition was observed in the human podocyte cell line and its effect on LN was evaluated in NZB/W F1 mice. In the human podocyte cell line, PCG potently inhibited PAR2 (IC50 = 1.5 ± 0.03 µM) and significantly reduced the PAR2-mediated activation of ERK1/2 and NF-κB signaling pathway. In addition, PCG significantly decreased PAR2-induced increases in ICAM-1 and VCAM-1 as well as in IL-8, IFN-γ, and TNF-α expression. Notably, the intraperitoneal administration of PCG significantly alleviated kidney injury and splenomegaly and reduced proteinuria and renal ICAM-1 and VCAM-1 expression in NZB/W F1 mice. Our results suggest that PCG has beneficial effects on LN via inhibition of PAR2, and PCG is a potential therapeutic agent for LN.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
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.titlePunicalagin Ameliorates Lupus Nephritis via Inhibition of PAR2-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorYohan Seo-
dc.contributor.googleauthorChin Hee Mun-
dc.contributor.googleauthorSo-Hyeon Park-
dc.contributor.googleauthorDongkyu Jeon-
dc.contributor.googleauthorSu Jeong Kim-
dc.contributor.googleauthorTaejun Yoon-
dc.contributor.googleauthorEunhee Ko-
dc.contributor.googleauthorSungwoo Jo-
dc.contributor.googleauthorYong-Beom Park-
dc.contributor.googleauthorWan Namkung-
dc.contributor.googleauthorSang-Won Lee-
dc.identifier.doi10.3390/ijms21144975-
dc.contributor.localIdA01579-
dc.contributor.localIdA02824-
dc.relation.journalcodeJ01133-
dc.identifier.eissn1422-0067-
dc.identifier.pmid32674502-
dc.subject.keywordNZB/W F1 mice-
dc.subject.keywordPAR2-
dc.subject.keywordlupus nephritis-
dc.subject.keywordpodocyte-
dc.subject.keywordpunicalagin-
dc.subject.keywordsystemic lupus erythematosus-
dc.contributor.alternativeNamePark, Yong Beom-
dc.contributor.affiliatedAuthor박용범-
dc.contributor.affiliatedAuthor이상원-
dc.citation.volume21-
dc.citation.number14-
dc.citation.startPage4975-
dc.identifier.bibliographicCitationINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol.21(14) : 4975, 2020-07-
dc.identifier.rimsid67146-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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