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DC Field | Value | Language |
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dc.citation.endPage | 370 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 359 | - |
dc.citation.title | JOURNAL OF IMMUNOLOGY | - |
dc.citation.volume | 201 | - |
dc.contributor.author | Lee, Saseong | - |
dc.contributor.author | Kong, Jin-Sun | - |
dc.contributor.author | You, Sungyong | - |
dc.contributor.author | Kwon, H. Moo | - |
dc.contributor.author | Yoo, Seung-Ah | - |
dc.contributor.author | Cho, Chul-Soo | - |
dc.contributor.author | Kim, Wan-Uk | - |
dc.date.accessioned | 2023-12-21T20:37:05Z | - |
dc.date.available | 2023-12-21T20:37:05Z | - |
dc.date.created | 2018-10-10 | - |
dc.date.issued | 2018-07 | - |
dc.description.abstract | Fibroblast-like synoviocytes (FLSs) play a key role in the progression of rheumatoid arthritis (RA) as a primary component of invasive hypertrophied pannus. FLSs of RA patients (RA-FLSs) exhibit cancer-like features, including promigratory and proinvasive activities that largely contribute to joint cartilage and bone destruction. In this study, we hypothesized that the NF of activated T cell 5 (NFAT5), a transcription factor involving tumor invasiveness, would control the migration and invasion of RA-FLSs. Analyses of transcriptomes demonstrated the significant involvement of NFAT5 in locomotion of RA-FLSs and that tissue factor (TF; also known as coagulation factor III) and CCL2 were the major downstream target genes of NFAT5 involving FLS migration and invasion. In cultured RA-FLSs, IL-1 beta and TGF-beta increased TF and CCL2 expression by upregulating NFAT5 expression via p38 MAPK. Functional assays demonstrated that NFAT5-or TF-deficient RA-FLSs displayed decreased lamellipodia formation, cell migration, and invasion under IL-1 beta- or TGF-beta-stimulated conditions. Conversely, factor VIIa, a specific activator of TF, increased migration of RA-FLSs, which was blocked by NFAT5 knockdown. Recombinant CCL2 partially restored the decrease in migration and invasion of NFAT5-deficient RA-FLSs stimulated with IL-1 beta. NFAT5-knockout mouse FLSs also showed decreased expressions of TF and CCL2 and reduced cell migration. Moreover, KRN2, a specific inhibitor of NFAT5, suppressed migration of FLSs stimulated with TGF-beta. Conclusively, to our knowledge, this is the first study to provide evidence of a functional link between osmoprotective NFAT5 and TF in the migration and invasion of RA-FLSs and supports a role for NFAT5 blockade in the treatment of RA. | - |
dc.identifier.bibliographicCitation | JOURNAL OF IMMUNOLOGY, v.201, no.2, pp.359 - 370 | - |
dc.identifier.doi | 10.4049/jimmunol.1701097 | - |
dc.identifier.issn | 0022-1767 | - |
dc.identifier.scopusid | 2-s2.0-85049866396 | - |
dc.identifier.uri | https://scholarworks.unist.ac.kr/handle/201301/24953 | - |
dc.identifier.url | http://www.jimmunol.org/content/201/2/359 | - |
dc.identifier.wosid | 000443575100005 | - |
dc.language | 영어 | - |
dc.publisher | AMER ASSOC IMMUNOLOGISTS | - |
dc.title | Transcription Factor NFAT5 Promotes Migration and Invasion of Rheumatoid Synoviocytes via Coagulation Factor III and CCL2 | - |
dc.type | Article | - |
dc.description.isOpenAccess | FALSE | - |
dc.relation.journalWebOfScienceCategory | Immunology | - |
dc.relation.journalResearchArea | Immunology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.subject.keywordPlus | HYPERPLASIA | - |
dc.subject.keywordPlus | GROWTH-FACTOR-BETA | - |
dc.subject.keywordPlus | ENHANCER-BINDING PROTEIN | - |
dc.subject.keywordPlus | TISSUE FACTOR | - |
dc.subject.keywordPlus | SYNOVIAL INFLAMMATION | - |
dc.subject.keywordPlus | TGF-BETA | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | CELL-MIGRATION | - |
dc.subject.keywordPlus | ARTHRITIS | - |
dc.subject.keywordPlus | PATHWAY | - |
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