Inhibition of lysophosphatidic acid receptor ameliorates Sjogren's syndrome in NOD mice
DC Field | Value | Language |
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dc.contributor.author | Park, Eunhye | - |
dc.contributor.author | Kim, Donghee | - |
dc.contributor.author | Lee, Song Mi | - |
dc.contributor.author | Jun, Hee-Sook | - |
dc.date.available | 2020-02-27T18:44:40Z | - |
dc.date.created | 2020-02-06 | - |
dc.date.issued | 2017-04 | - |
dc.identifier.issn | 1949-2553 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/6221 | - |
dc.description.abstract | Lysophosphatidic acid (LPA), a bioactive lysophospholipid, is involved in the pathogenesis of chronic inflammatory and autoimmune diseases. In this study, we investigated the role of LPA/LPA receptor (LPAR) signaling in the pathogenesis of Sjogren's syndrome (SS). We found that autotaxin, an LPA producing enzyme, and LPAR1 and LPAR3 mRNA, and IL-17 mRNA were highly expressed in the exocrine glands of 20-week-old nonobese diabetic (NOD) mice, which show SS symptoms at this age, as compared with non-symptomatic 8-week-old NOD mice. In an adoptive transfer model using NOD lymphocytes, treatment with Ki16425, an LPAR1/3 antagonist, restored tear and saliva secretion and decreased symptoms of SS compared with the vehicle-treated group. IL-17 levels in serum and lacrimal glands were also significantly reduced by Ki16425 in recipient mice. In addition, Ki16425 treatment of 20-week-old NOD mice, which spontaneously developed SS, restored saliva volume. Treatment of NOD splenocytes with LPA induced the expression of IL-17 in a dose-dependent manner, and Ki16425 inhibited this increase. LPA stimulated the activation of ROCK2 and p38 MAPK; and inhibition of ROCK2 or p38 MAPK suppressed LPA-induced IL-17 expression. Our data suggest that LPAR signaling stimulates SS development by induction of IL-17 production via ROCK and p38 MAPK pathways. Thus, LPAR inhibition could be a possible therapeutic strategy for SS. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | IMPACT JOURNALS LLC | - |
dc.relation.isPartOf | ONCOTARGET | - |
dc.title | Inhibition of lysophosphatidic acid receptor ameliorates Sjogren's syndrome in NOD mice | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000399819700115 | - |
dc.identifier.doi | 10.18632/oncotarget.15916 | - |
dc.identifier.bibliographicCitation | ONCOTARGET, v.8, no.16, pp.27240 - 27251 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85017519608 | - |
dc.citation.endPage | 27251 | - |
dc.citation.startPage | 27240 | - |
dc.citation.title | ONCOTARGET | - |
dc.citation.volume | 8 | - |
dc.citation.number | 16 | - |
dc.contributor.affiliatedAuthor | Park, Eunhye | - |
dc.contributor.affiliatedAuthor | Kim, Donghee | - |
dc.contributor.affiliatedAuthor | Lee, Song Mi | - |
dc.contributor.affiliatedAuthor | Jun, Hee-Sook | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Sjogren&apos | - |
dc.subject.keywordAuthor | s syndrome | - |
dc.subject.keywordAuthor | LPA | - |
dc.subject.keywordAuthor | Ki16425 | - |
dc.subject.keywordAuthor | NOD mice | - |
dc.subject.keywordAuthor | IL-17 | - |
dc.subject.keywordPlus | SALIVARY-GLAND | - |
dc.subject.keywordPlus | P38 MAPK | - |
dc.subject.keywordPlus | T-CELLS | - |
dc.subject.keywordPlus | DRY EYE | - |
dc.subject.keywordPlus | SECRETION | - |
dc.subject.keywordPlus | AUTOTAXIN | - |
dc.subject.keywordPlus | DIFFERENTIATION | - |
dc.subject.keywordPlus | INFLAMMATION | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | MIGRATION | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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