Abstract | Purpose: Methods: Results: Expression levels of S1PR mRNA and S1P 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 profibrotic stimulants upregulated collagen Iα, fibronectin, α-SMA, MMP-1, MMP-2, MMP-9, and TIMP-1 expression in a dose-dependent manner. Conclusions: 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.
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Authors | JaeSang Ko, Min Kyoung Chae, Joon H Lee, Eun Jig Lee, Jin Sook Yoon |
Journal | Investigative ophthalmology & visual science
(Invest Ophthalmol Vis Sci)
Vol. 58
Issue 5
Pg. 2544-2553
(05 01 2017)
ISSN: 1552-5783 [Electronic] United States |
PMID | 28492873
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Lysophospholipids
- sphingosine 1-phosphate
- RNA
- Sphingosine
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Topics |
- Adult
- Blotting, Western
- Cells, Cultured
- Female
- Fibroblasts
(metabolism, pathology)
- Fibrosis
(genetics, metabolism, pathology)
- Gene Expression Regulation
- Graves Ophthalmopathy
(genetics, metabolism, pathology)
- Humans
- Lysophospholipids
(biosynthesis, genetics)
- Male
- Middle Aged
- RNA
(genetics)
- Real-Time Polymerase Chain Reaction
- Signal Transduction
- Sphingosine
(analogs & derivatives, biosynthesis, genetics)
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