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Int. J. Mol. Sci. 2018, 19(1), 112; https://doi.org/10.3390/ijms19010112

Apolipoprotein M Inhibits Angiogenic and Inflammatory Response by Sphingosine 1-Phosphate on Retinal Pigment Epithelium Cells

Department of Ophthalmology, Graduate School of Medicine, Tokyo University, Tokyo 113-8654, Japan
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Received: 27 October 2017 / Revised: 20 December 2017 / Accepted: 28 December 2017 / Published: 31 December 2017
(This article belongs to the Special Issue Sphingolipids: Signals and Disease)
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Abstract

Sphingosine 1-phosphate (S1P) is a potent lipid mediator that modulates inflammatory responses and proangiogenic factors. It has been suggested that S1P upregulates choroidal neovascularization (CNV) and may be deeply involved in the pathogenesis of exudative age-related macular degeneration (AMD). Recent studies have suggested that apolipoprotein M (ApoM), a carrier protein for S1P, modulates the biological properties of S1P in the pathogenesis of atherosclerosis. However, the role of ApoM/S1P in AMD has not been explored. We investigated the effect of S1P on proangiogenic factors in human retinal pigment epithelium (RPE) cell lines in vitro. S1P promoted the expression of vascular endothelial growth factor in RPE cells. Hypoxia inducible factor-1α expression was also upregulated. These S1P-induced enhancements in growth factors and chemotactic cytokines in RPE cells were significantly inhibited by ApoM treatment. Additionally, in vivo experiments using a laser-induced CNV murine model demonstrated that intravitreal ApoM injection significantly reduced the progression of CNV formation. Although the detailed mechanisms remain to be elucidated, the present results provide a novel potential therapeutic target for AMD, and demonstrate a suppressive role for ApoM and S1P in the pathology of CNV progression. View Full-Text
Keywords: sphingosine 1-phosphate; sphingolipids and inflammation; S1P-receptors; apolipoprotein M; high-density lipoprotein; choroidal neovascularization; age-related macular degeneration; vascular endothelial growth factor; hypoxia inducible factor; interleukin-8 sphingosine 1-phosphate; sphingolipids and inflammation; S1P-receptors; apolipoprotein M; high-density lipoprotein; choroidal neovascularization; age-related macular degeneration; vascular endothelial growth factor; hypoxia inducible factor; interleukin-8
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Terao, R.; Honjo, M.; Aihara, M. Apolipoprotein M Inhibits Angiogenic and Inflammatory Response by Sphingosine 1-Phosphate on Retinal Pigment Epithelium Cells. Int. J. Mol. Sci. 2018, 19, 112.

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