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The Role of Sphingosine-1-Phosphate in Adipogenesis of Graves' Orbitopathy.

Authors
 Sung Eun Kim  ;  Joon H. Lee  ;  Min Kyoung Chae  ;  Eun Jig Lee  ;  Jin Sook Yoon 
Citation
 Investigative Ophthalmology & Visual Science, Vol.57(2) : 301-311, 2016 
Journal Title
 Investigative Ophthalmology & Visual Science 
ISSN
 0146-0404 
Issue Date
2016
MeSH
Adipogenesis/physiology* ; Adult ; Blotting, Western ; CCAAT-Enhancer-Binding Protein-beta/metabolism ; CCAAT-Enhancer-Binding Proteins/metabolism ; Cell Differentiation ; Cells, Cultured ; Female ; Fibroblasts/physiology ; Fingolimod Hydrochloride/pharmacology ; Graves Ophthalmopathy/metabolism* ; Humans ; Immunosuppressive Agents/pharmacology ; Lysophospholipids/physiology* ; Male ; Middle Aged ; Orbit/cytology ; PPAR gamma/metabolism ; RNA, Messenger/genetics ; Reactive Oxygen Species/metabolism ; Real-Time Polymerase Chain Reaction ; Receptors, Lysosphingolipid/antagonists & inhibitors ; Receptors, Lysosphingolipid/genetics ; Sphingosine/analogs & derivatives* ; Sphingosine/physiology
Keywords
sphingosine-1-phosphate ; Graves’ orbitopathy ; adipogenesis
Abstract
PURPOSE: To investigate the action of sphingosine-1-phosphate (S1P) in adipocyte differentiation of orbital fibroblasts and determine its putative role in the pathogenesis of Graves' orbitopathy (GO). METHODS: Primary preadipocyte orbital fibroblast cultures were stimulated for adipogenesis. Real-time PCR was performed to evaluate the expression of S1P receptor mRNA. To evaluate the effect of S1P and S1P receptor blockers (W146 and FTY720) on adipocyte differentiation, cultures were exposed to each receptor blocker for the first 4 days of the differentiation period. Differentiated cells were stained with Oil Red O, and the production of peroxisome proliferator activator gamma (PPARγ) and CCAAT-enhancer-binding proteins (C/EBP) α and β were determined by Western blot analysis. RESULTS: Sphingosine-1-phosphate receptor 1, 2, and 3 mRNA expression levels were significantly higher in GO tissue samples than non-GO. Sphingosine-1-phosphate receptor 1 through 5 mRNA expression was significantly increased during the 10 days of adipogenesis. Sphingosine-1-phosphate treatment increased the size and number of adipocytes, and increased the expression of adipogenic transcriptional regulators. Treatment with S1P1 receptor inhibitor (W146) for 4 days after induction of adipogenesis attenuated adipocyte differentiation. Sphingosine-1-phosphate receptor blocker also decreased reactive oxygen species (ROS) production in GO orbital fibroblasts and H2O2-stimulated HO-1 production in GO orbital fibroblasts. S1P1 receptor inhibitor reduced the number of adipocytes and suppressed the accumulation of lipid droplets induced by 10 μM H2O2 or 2% cigarette smoke extract (CSE) treatment. CONCLUSIONS: Sphingosine-1-phosphate could play a role in orbital adipocyte differentiation of GO. Modulation of S1P actions may provide a therapeutic target for the treatment of GO.
Files in This Item:
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DOI
10.1167/iovs.15-17863
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
윤진숙(Yoon, Jin Sook) ORCID logo https://orcid.org/0000-0002-8751-9467
이은직(Lee, Eun Jig) ORCID logo https://orcid.org/0000-0002-9876-8370
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/146405
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