Cited 7 times in
Glycogen Synthase Kinase-3β Mediates Proinflammatory Cytokine Secretion and Adipogenesis in Orbital Fibroblasts from Patients with Graves’ Orbitopathy
DC Field | Value | Language |
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dc.contributor.author | 이은직 | - |
dc.contributor.author | 윤진숙 | - |
dc.date.accessioned | 2020-09-29T01:41:22Z | - |
dc.date.available | 2020-09-29T01:41:22Z | - |
dc.date.issued | 2020-07 | - |
dc.identifier.issn | 0146-0404 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/179480 | - |
dc.description.abstract | Purpose: We sought to determine the role of glycogen synthase kinase-3β (GSK-3β) in the pathogenesis of Graves' orbitopathy(GO). Methods: Expression of the GSK-3β gene in whole orbital tissue explants was compared between GO and non-GO donors using quantitative real-time PCR (RT-PCR). The expression of proinflammatory molecules in the presence of the GSK-3β inhibitor CHIR 99021 was analyzed using RT-PCR, western blot, and ELISA. Adipogenic differentiation was identified using Oil Red O staining, and the levels of peroxisome proliferator activator gamma (PPARγ) and CCAAT-enhancer-binding proteins (C/EBPs) α and β were determined by western blot. Results: The expression of GSK-3β was significantly higher in GO tissues than in control tissues. The addition of CHIR 99021 led to a decrease in the active form of the kinase in which the Y216 residue is phosphorylated. When GO and non-GO fibroblasts were stimulated with IL-1β or TNF-α, IL-6, IL-8, intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-1 (COX-1), and monocyte chemoattractant protein 1 (MCP-1) showed increased production, which was blunted when CHIR 99021 was added. The activation of Akt, PI3K, nuclear factor (NF)-κB, Erk, Jnk, and p38 kinase by IL-1β and TNF-α was diminished with CHIR 99021 in GO cells. A decrease in lipid droplets and expression of PPARγ and c/EBPα and -β was noted in fibroblasts treated with CHIR 99021 during adipocyte differentiation. The inhibition of Wnt and β-catenin in adipogenesis was reversed by CHIR 99021. Conclusions: GSK-3β plays a significant role in GO pathogenesis. The inhibition of the kinase attenuated the proinflammatory cytokines production and fibroblast differentiation into adipocytes. GSK-3β may be a potential target for anti-inflammatory and anti-adipogenic treatment of GO. | - |
dc.description.statementOfResponsibility | open | - |
dc.language | English | - |
dc.publisher | Association For Research In Vision And Ophthalmology (Arvo) | - |
dc.relation.isPartOf | INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | Glycogen Synthase Kinase-3β Mediates Proinflammatory Cytokine Secretion and Adipogenesis in Orbital Fibroblasts from Patients with Graves’ Orbitopathy | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Jihei Sara Lee | - |
dc.contributor.googleauthor | Min Kyoung Chae | - |
dc.contributor.googleauthor | Don O Kikkawa | - |
dc.contributor.googleauthor | Eun Jig Lee | - |
dc.contributor.googleauthor | Jin Sook Yoon | - |
dc.identifier.doi | 10.1167/iovs.61.8.51 | - |
dc.contributor.localId | A03050 | - |
dc.contributor.localId | A02611 | - |
dc.relation.journalcode | J01187 | - |
dc.identifier.eissn | 1552-5783 | - |
dc.identifier.pmid | 32735324 | - |
dc.contributor.alternativeName | Lee, Eun Jig | - |
dc.contributor.affiliatedAuthor | 이은직 | - |
dc.contributor.affiliatedAuthor | 윤진숙 | - |
dc.citation.volume | 61 | - |
dc.citation.number | 8 | - |
dc.citation.startPage | 51 | - |
dc.identifier.bibliographicCitation | INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, Vol.61(8) : 51, 2020-07 | - |
dc.identifier.rimsid | 67137 | - |
dc.type.rims | ART | - |
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