Sphingosine-1-phosphate is a crucial signal for migration of retina Müller glial cells

Autores
Simon, Maria Victoria; Prado Spalm, Facundo H.; Politi, Luis Enrique; Rotstein, Nora Patricia
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
PURPOSE. Migration of M¨uller 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. M¨uller glial cell cultures from rat retinas were supplemented with 5 lM 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 M¨uller 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-activatedprotein 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 M¨uller 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 fortreating these diseases.
Fil: Simon, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Prado Spalm, Facundo H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Politi, Luis Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Rotstein, Nora Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Materia
Sphingosine 1 Phosphate
Receptor
Retina
Gliosis
Proliferative Retinopathies
Müller Glial Cells
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/4382
Acceder
id CONICETDig_fd5bf276e77bac328ed2b860b83860b0
oai_identifier_str oai:ri.conicet.gov.ar:11336/4382
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Sphingosine-1-phosphate is a crucial signal for migration of retina Müller glial cellsSimon, Maria VictoriaPrado Spalm, Facundo H.Politi, Luis EnriqueRotstein, Nora PatriciaSphingosine 1 PhosphateReceptorRetinaGliosisProliferative RetinopathiesMüller Glial Cellshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1PURPOSE. Migration of M¨uller 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. M¨uller glial cell cultures from rat retinas were supplemented with 5 lM 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 M¨uller 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-activatedprotein 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 M¨uller 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 fortreating these diseases.Fil: Simon, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaFil: Prado Spalm, Facundo H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); ArgentinaFil: Politi, Luis Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaFil: Rotstein, Nora Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina. Universidad Nacional del Sur; ArgentinaAssociation For Research In Vision And Ophthalmology2015-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/4382Simon, Maria Victoria; Prado Spalm, Facundo H.; Politi, Luis Enrique; Rotstein, Nora Patricia; Sphingosine-1-phosphate is a crucial signal for migration of retina Müller glial cells; Association For Research In Vision And Ophthalmology; Investigative Ophthalmology & Visual Science; 56; 7-2015; 5808-58150146-0404enginfo:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/altIdentifier/url/http://iovs.arvojournals.org/article.aspx?articleid=2433280info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.1167/ iovs.14-16195info:eu-repo/semantics/altIdentifier/url/http://www.iovs.org/site/misc/author.xhtmlinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:56:49Zoai:ri.conicet.gov.ar:11336/4382instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:56:49.785CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Sphingosine-1-phosphate is a crucial signal for migration of retina Müller glial cells
title Sphingosine-1-phosphate is a crucial signal for migration of retina Müller glial cells
spellingShingle Sphingosine-1-phosphate is a crucial signal for migration of retina Müller glial cells
Simon, Maria Victoria
Sphingosine 1 Phosphate
Receptor
Retina
Gliosis
Proliferative Retinopathies
Müller Glial Cells
title_short Sphingosine-1-phosphate is a crucial signal for migration of retina Müller glial cells
title_full Sphingosine-1-phosphate is a crucial signal for migration of retina Müller glial cells
title_fullStr Sphingosine-1-phosphate is a crucial signal for migration of retina Müller glial cells
title_full_unstemmed Sphingosine-1-phosphate is a crucial signal for migration of retina Müller glial cells
title_sort Sphingosine-1-phosphate is a crucial signal for migration of retina Müller glial cells
dc.creator.none.fl_str_mv Simon, Maria Victoria
Prado Spalm, Facundo H.
Politi, Luis Enrique
Rotstein, Nora Patricia
author Simon, Maria Victoria
author_facet Simon, Maria Victoria
Prado Spalm, Facundo H.
Politi, Luis Enrique
Rotstein, Nora Patricia
author_role author
author2 Prado Spalm, Facundo H.
Politi, Luis Enrique
Rotstein, Nora Patricia
author2_role author
author
author
dc.subject.none.fl_str_mv Sphingosine 1 Phosphate
Receptor
Retina
Gliosis
Proliferative Retinopathies
Müller Glial Cells
topic Sphingosine 1 Phosphate
Receptor
Retina
Gliosis
Proliferative Retinopathies
Müller Glial Cells
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv PURPOSE. Migration of M¨uller 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. M¨uller glial cell cultures from rat retinas were supplemented with 5 lM 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 M¨uller 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-activatedprotein 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 M¨uller 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 fortreating these diseases.
Fil: Simon, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Prado Spalm, Facundo H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina
Fil: Politi, Luis Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
Fil: Rotstein, Nora Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico CONICET Bahía Blanca. Instituto de Investigaciones Bioquímicas Bahía Blanca (i); Argentina. Universidad Nacional del Sur; Argentina
description PURPOSE. Migration of M¨uller 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. M¨uller glial cell cultures from rat retinas were supplemented with 5 lM 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 M¨uller 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-activatedprotein 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 M¨uller 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 fortreating these diseases.
publishDate 2015
dc.date.none.fl_str_mv 2015-07
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/4382
Simon, Maria Victoria; Prado Spalm, Facundo H.; Politi, Luis Enrique; Rotstein, Nora Patricia; Sphingosine-1-phosphate is a crucial signal for migration of retina Müller glial cells; Association For Research In Vision And Ophthalmology; Investigative Ophthalmology & Visual Science; 56; 7-2015; 5808-5815
0146-0404
url http://hdl.handle.net/11336/4382
identifier_str_mv Simon, Maria Victoria; Prado Spalm, Facundo H.; Politi, Luis Enrique; Rotstein, Nora Patricia; Sphingosine-1-phosphate is a crucial signal for migration of retina Müller glial cells; Association For Research In Vision And Ophthalmology; Investigative Ophthalmology & Visual Science; 56; 7-2015; 5808-5815
0146-0404
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/
info:eu-repo/semantics/altIdentifier/url/http://iovs.arvojournals.org/article.aspx?articleid=2433280
info:eu-repo/semantics/altIdentifier/url/http://dx.doi.org/10.1167/ iovs.14-16195
info:eu-repo/semantics/altIdentifier/url/http://www.iovs.org/site/misc/author.xhtml
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Association For Research In Vision And Ophthalmology
publisher.none.fl_str_mv Association For Research In Vision And Ophthalmology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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