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

International Journal of Molecular Sciences
Ryo TeraoMakoto Aihara

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 demonst...Continue Reading

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Citations

Aug 10, 2019·Kardiologiia·A V AlessenkoI N Kurochkin
Apr 23, 2019·Current Opinion in Lipidology·Line S Bisgaard, Christina Christoffersen
Jun 28, 2019·Frontiers in Cellular Neuroscience·M Victoria SimónNora P Rotstein
Jul 31, 2019·International Journal of Molecular Sciences·Ryo TeraoMakoto Aihara
Jul 9, 2020·International Journal of Molecular Sciences·Ryo Terao, Hiroki Kaneko
Sep 20, 2020·Journal of Lipid Research·M Victoria SimonNawajes Mandal
Feb 9, 2021·Journal of Lipid Research·Simon M VictoriaMandal Nawajes
Nov 18, 2021·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Michael Landowski, Catherine Bowes Rickman

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Methods Mentioned

BETA
PCR
enzyme-linked immunosorbent assay
ELISA
Protein Assay

Software Mentioned

ImageJ

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