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Sphingosine-1-phosphate mediates fibrosis in orbital fibroblasts in graves’ orbitopathy

DC FieldValueLanguage
dc.contributor.author고재상-
dc.date.accessioned2019-01-02T16:45:45Z-
dc.date.available2019-01-02T16:45:45Z-
dc.date.issued2018-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/166449-
dc.description의학과/박사-
dc.description.abstractPurpose: To investigate the effect of sphingosine-1-phosphate (S1P) on fibrosis in orbital fibroblasts in Graves’ orbitopathy (GO). Methods: Orbital fibroblasts were cultured from orbital adipose/connective tissues of patients with GO and healthy control subjects. Effects of treatment with transforming growth factor (TGF)-β and cigarette smoke extract (CSE) on S1P receptor (S1PR) messenger RNAs (mRNA) were evaluated by real-time polymerase chain reaction. To evaluate the role of S1P in fibrosis, cells were pretreated with W146 (S1PR1 antagonist), JTE013 (S1PR2 antagonist), FTY720 (S1PR1 modulator), or 5C (sphingosine kinase-1 blocker) for 1 h before stimulation with TGF-β, CSE, or interleukin (IL)-1β. Expression of fibrosis-related proteins—collagen Iα, fibronectin, and α-smooth muscle actin (SMA)—and tissue remodeling-related proteins—matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase (TIMP)-1—was then evaluated by Western blotting. Results: Expression levels of S1PR mRNAs in GO orbital fibroblasts increased upon TGF-β and CSE treatment. Treatment with S1PR blockers and 5C inhibited TGF-β and CSE-induced expression of collagen Iα, fibronectin, and α-SMA as well as IL-1β-induced expression of MMP-1, MMP-2, MMP-9, and TIMP-1. Exogenous S1P treatment without pro-fibrotic stimulants upregulated collagen Iα, fibronectin, α-SMA, MMP-1, MMP-2, MMP-9, and TIMP-1 expression in a dose-dependent manner. Conclusion: Blocking of S1PR activity and inhibition of S1P synthesis led to decreased expression of fibrosis and tissue remodeling-related proteins in primary cultures of orbital fibroblasts derived from patients with GO. Thus, modulation of S1P activity might have therapeutic potential in the suppression of fibrosis in GO.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.publisher연세대학교-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleSphingosine-1-phosphate mediates fibrosis in orbital fibroblasts in graves’ orbitopathy-
dc.title.alternative갑상샘눈병증 환자의 안와 섬유모세포에서 섬유화에 대한 sphingosine-1-phosphate의 역할-
dc.typeThesis-
dc.contributor.departmentDept. of Ophthalmology (안과학교실)-
dc.contributor.localIdA04876-
dc.description.degree박사-
dc.contributor.alternativeNameKo, JaeSang-
dc.contributor.affiliatedAuthor고재상-
dc.type.localDissertation-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 3. Dissertation

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