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PERK mediates oxidative stress and adipogenesis in Graves' orbitopathy pathogenesis

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dc.contributor.author고재상-
dc.contributor.author윤진숙-
dc.contributor.author이은직-
dc.date.accessioned2021-09-29T01:14:36Z-
dc.date.available2021-09-29T01:14:36Z-
dc.date.issued2021-05-
dc.identifier.issn0952-5041-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/184264-
dc.description.abstractWe examined endoplasmic reticulum (ER) stress-related gene expression in orbital tissues from patients with Graves' orbitopathy (GO) and the effects of silencing protein kinase RNA-like endoplasmic reticulum kinase (PERK) in primary orbital fibroblast cultures to demonstrate the therapeutic potential of PERK-modulating agents in GO management. The expression of ER stress-related genes in orbital tissue harvested from individuals with or without GO was studied using real-time PCR. The role of PERK in GO pathogenesis was examined through small-interfering RNA (siRNA)-mediated silencing in cultured primary orbital fibroblasts. Intracellular reactive oxygen species (ROS) levels induced in response to cigarette smoke extract (CSE) or hydrogen peroxide were measured using 5-(and 6)-carboxy-20,70-dichlorodihydrofluorescein diacetate staining and flow cytometry. Cells were stained with Oil Red O, and adipogenesis-related transcription factor expression was evaluated through Wwestern blotting after adipogenic differentiation. PERK, activating transcription factor 4 (ATF4), and CCAAT-enhancer-binding protein (C/EBP)-homologous protein (CHOP) mRNA levels were significantly higher in GO orbital tissues than in non-GO orbital tissues. PERK silencing inhibited CSE- or hydrogen peroxide-induced ROS generation. After adipogenic differentiation, GO orbital fibroblasts revealed decreased lipid droplets and downregulation of C/EBPα, C/EBPβ, and peroxisome proliferator-activator gamma (PPARγ) in PERK siRNA-transfected cells. The orbital tissues of patients with GO were exposed to chronic ER stress and subsequently exhibited enhanced unfolded protein response (especially through the PERK pathway). PERK silencing reduced oxidative stress and adipogenesis in GO orbital fibroblasts in vitro. Our results imply that PERK-modulating agents can potentially be used to manage GO.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherBioScientifica-
dc.relation.isPartOfJOURNAL OF MOLECULAR ENDOCRINOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titlePERK mediates oxidative stress and adipogenesis in Graves' orbitopathy pathogenesis-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Ophthalmology (안과학교실)-
dc.contributor.googleauthorJaeSang Ko-
dc.contributor.googleauthorJi-Young Kim-
dc.contributor.googleauthorMin Kyoung Chae-
dc.contributor.googleauthorEun Jig Lee-
dc.contributor.googleauthorJin Sook Yoon-
dc.identifier.doi10.1530/JME-21-0057-
dc.contributor.localIdA04876-
dc.contributor.localIdA02611-
dc.contributor.localIdA03050-
dc.relation.journalcodeJ01606-
dc.identifier.eissn1479-6813-
dc.identifier.pmid33870911-
dc.identifier.urlhttps://jme.bioscientifica.com/view/journals/jme/66/4/JME-21-0057.xml-
dc.subject.keywordGraves’ orbitopathy-
dc.subject.keywordPERK-
dc.subject.keywordendoplasmic reticulum stress-
dc.subject.keywordprotein kinase RNA-like endoplasmic reticulum kinase-
dc.subject.keywordthyroid eye disease-
dc.contributor.alternativeNameKo, Jaesang-
dc.contributor.affiliatedAuthor고재상-
dc.contributor.affiliatedAuthor윤진숙-
dc.contributor.affiliatedAuthor이은직-
dc.citation.volume66-
dc.citation.number4-
dc.citation.startPage313-
dc.citation.endPage323-
dc.identifier.bibliographicCitationJOURNAL OF MOLECULAR ENDOCRINOLOGY, Vol.66(4) : 313-323, 2021-05-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers

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