Abstract:
PURPOSE:Migration of Müller glial cells is enhanced in proliferative retinopathies, but the mechanisms involved are ill defined. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid synthesized by sphingosine kinase (SphK), which promotes proliferation, migration, and inflammation, acting as an intracellular mediator and activating a family of membrane receptors (S1PRs). We investigated whether S1P regulated glial migration. METHODS:Müller glial cell cultures from rat retinas were supplemented with 5 μM S1P, and migration was evaluated by scratch-wound assays. Cultures were treated with SphK inhibitor 2 (SphKI 2), a SphK1 inhibitor, or with W146 and BML-241, S1P1 and S1P3 antagonists, respectively, to investigate whether Müller glial cells synthesized S1P and S1P-activated S1PRs to stimulate migration. The effects of LY294002, U0126, and SB203580, which are phosphatidylinositol-3 kinase (PI3K), extracellular signal regulated kinase/mitogen-activated protein kinase (ERK/MAPK), and p38 MAPK inhibitors, respectively, on glial migration were determined. RESULTS:Sphingosine-1-phosphate addition prompted the formation of lamellipodia and enhanced glial migration. SphKI 2 almost completely prevented glial migration in controls; BML-241 inhibited this migration both in controls and in S1P-supplemented cultures, whereas W146 had no significant effect. Pretreatment with LY294002 and U0126 abrogated glial migration; SB203580 decreased it partially, although not significantly. CONCLUSIONS:Our results suggest that Müller glial cells synthesize S1P, which signals through S1P3 and the PI3K and ERK/MAPK pathways to induce glial migration. As a whole, our data point to a central role for S1P in controlling glial cell motility. Because deregulation of this process is involved in several retinal pathologies, S1P signaling emerges as a potential tool for treating these diseases.
journal_name
Invest Ophthalmol Vis Scijournal_title
Investigative ophthalmology & visual scienceauthors
Simón MV,Prado Spalm FH,Politi LE,Rotstein NPdoi
10.1167/iovs.14-16195subject
Has Abstractpub_date
2015-09-01 00:00:00pages
5808-15issue
10eissn
0146-0404issn
1552-5783pii
2433280journal_volume
56pub_type
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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更新日期:2018-11-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
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journal_title:Investigative ophthalmology & visual science
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doi:
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doi:
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更新日期:2010-11-01 00:00:00
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doi:
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更新日期:2009-09-01 00:00:00
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journal_title:Investigative ophthalmology & visual science
pub_type: 杂志文章
doi:
更新日期:1992-08-01 00:00:00
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