Recruiting sphingolipids to promote migration of retinal pigment epithelium cells

Autores
Simon, Maria Victoria; Vera, Marcela Sonia; Rotstein, Nora Patricia
Año de publicación
2019
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Retinal proliferative diseases, frequent causes of vision loss, involve excessive migration and proliferation of Müller glial cells (MGC) and retinal pigmented epithelium (RPE) cells. Bioactive sphingolipids, as sphingosine-1- phosphate (S1P) and ceramide-1-phosphate (C1P), are established mediators of inflammation and fibrosis and we have shown that S1P stimulates MGC migration (Simon et al; 2015). We now analyzed if they promote RPE migration. We supplemented ARPE19 cells, a human RPE cell line, with 5 μM S1P or 10 μM C1P. We pretreated them with SphkI2 or NVP, inhibitors of sphingosine kinase-1 (SphK1) and ceramide kinase (CerK), respectively to analyze if endogenous S1P or C1P stimulate cell migration, and with W146 and BML241, S1P1 and S1P3 antagonists, respectively to investigate if S1P activated these receptors. Migration was analyzed by the scratch wound assay. Exogenous S1P or C1P significantly promoted RPE cell migration, but their combined addition had no additive effect. Inhibiting S1P synthesis significantly reduced cell migration, and exogenous S1P and C1P partially restored it. In contrast, NVP treatment had no effect on RPE migration. Pretreatment with W146 reduced RPE migration both in control and S1P- supplemented cultures, while BML241 only reduced it in S1P- treated cultures. Our results suggest that endogenous synthesis of S1P activates S1P1 to induce RPE cell migration whereas exogenous S1P stimulates migration by activating both S1P1 and S1P3. Notably, exogenous C1P enhances RPE cell migration but its endogenous synthesis does not. Noteworthy, when added together, S1P and C1P had the same effect on migration as when added separately, implying they may share common signaling pathways. Hence, sphingolipids appear as central regulators of cell migration, and targeting their metabolism might provide tools for treating proliferative retinopathies.
Fil: Simon, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Vera, Marcela Sonia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Rotstein, Nora Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Reunión Anual de Sociedades de Biociencia 2019; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); XXI Reunión Anual de la Sociedad Argentina de Biología (SAB); XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP); IX Reunión Anual de la Asociación Argentina de Nanomedicinas (NANOMED-ar); VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACyTAL)
Mar del Plata, Buenos Aires
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
The Histochemical Society
Materia
ESFINGOSINA 1 FOSFATO
RETINA
MIGRACION
EPITELIO PIGMENTADO
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/188866
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Recruiting sphingolipids to promote migration of retinal pigment epithelium cellsSimon, Maria VictoriaVera, Marcela SoniaRotstein, Nora PatriciaESFINGOSINA 1 FOSFATORETINAMIGRACIONEPITELIO PIGMENTADOhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Retinal proliferative diseases, frequent causes of vision loss, involve excessive migration and proliferation of Müller glial cells (MGC) and retinal pigmented epithelium (RPE) cells. Bioactive sphingolipids, as sphingosine-1- phosphate (S1P) and ceramide-1-phosphate (C1P), are established mediators of inflammation and fibrosis and we have shown that S1P stimulates MGC migration (Simon et al; 2015). We now analyzed if they promote RPE migration. We supplemented ARPE19 cells, a human RPE cell line, with 5 μM S1P or 10 μM C1P. We pretreated them with SphkI2 or NVP, inhibitors of sphingosine kinase-1 (SphK1) and ceramide kinase (CerK), respectively to analyze if endogenous S1P or C1P stimulate cell migration, and with W146 and BML241, S1P1 and S1P3 antagonists, respectively to investigate if S1P activated these receptors. Migration was analyzed by the scratch wound assay. Exogenous S1P or C1P significantly promoted RPE cell migration, but their combined addition had no additive effect. Inhibiting S1P synthesis significantly reduced cell migration, and exogenous S1P and C1P partially restored it. In contrast, NVP treatment had no effect on RPE migration. Pretreatment with W146 reduced RPE migration both in control and S1P- supplemented cultures, while BML241 only reduced it in S1P- treated cultures. Our results suggest that endogenous synthesis of S1P activates S1P1 to induce RPE cell migration whereas exogenous S1P stimulates migration by activating both S1P1 and S1P3. Notably, exogenous C1P enhances RPE cell migration but its endogenous synthesis does not. Noteworthy, when added together, S1P and C1P had the same effect on migration as when added separately, implying they may share common signaling pathways. Hence, sphingolipids appear as central regulators of cell migration, and targeting their metabolism might provide tools for treating proliferative retinopathies.Fil: Simon, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Vera, Marcela Sonia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Rotstein, Nora Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaReunión Anual de Sociedades de Biociencia 2019; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); XXI Reunión Anual de la Sociedad Argentina de Biología (SAB); XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP); IX Reunión Anual de la Asociación Argentina de Nanomedicinas (NANOMED-ar); VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACyTAL)Mar del Plata, Buenos AiresArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioThe Histochemical SocietyMedicina (Buenos Aires)Kotsias, Basilio Aristidesde Vito, EduardoNarvaiz Kantor, IsabelSemeniuk, Guillermo Basilio2019info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/188866Recruiting sphingolipids to promote migration of retinal pigment epithelium cells; Reunión Anual de Sociedades de Biociencia 2019; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); XXI Reunión Anual de la Sociedad Argentina de Biología (SAB); XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP); IX Reunión Anual de la Asociación Argentina de Nanomedicinas (NANOMED-ar); VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACyTAL); Mar del Plata, Buenos Aires; Argentina; 2019; 176-1770025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.saic.org.ar/revista-medicinaNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:04:03Zoai:ri.conicet.gov.ar:11336/188866instacron: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:34982025-09-10 13:04:03.506CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Recruiting sphingolipids to promote migration of retinal pigment epithelium cells
title Recruiting sphingolipids to promote migration of retinal pigment epithelium cells
spellingShingle Recruiting sphingolipids to promote migration of retinal pigment epithelium cells
Simon, Maria Victoria
ESFINGOSINA 1 FOSFATO
RETINA
MIGRACION
EPITELIO PIGMENTADO
title_short Recruiting sphingolipids to promote migration of retinal pigment epithelium cells
title_full Recruiting sphingolipids to promote migration of retinal pigment epithelium cells
title_fullStr Recruiting sphingolipids to promote migration of retinal pigment epithelium cells
title_full_unstemmed Recruiting sphingolipids to promote migration of retinal pigment epithelium cells
title_sort Recruiting sphingolipids to promote migration of retinal pigment epithelium cells
dc.creator.none.fl_str_mv Simon, Maria Victoria
Vera, Marcela Sonia
Rotstein, Nora Patricia
author Simon, Maria Victoria
author_facet Simon, Maria Victoria
Vera, Marcela Sonia
Rotstein, Nora Patricia
author_role author
author2 Vera, Marcela Sonia
Rotstein, Nora Patricia
author2_role author
author
dc.contributor.none.fl_str_mv Kotsias, Basilio Aristides
de Vito, Eduardo
Narvaiz Kantor, Isabel
Semeniuk, Guillermo Basilio
dc.subject.none.fl_str_mv ESFINGOSINA 1 FOSFATO
RETINA
MIGRACION
EPITELIO PIGMENTADO
topic ESFINGOSINA 1 FOSFATO
RETINA
MIGRACION
EPITELIO PIGMENTADO
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Retinal proliferative diseases, frequent causes of vision loss, involve excessive migration and proliferation of Müller glial cells (MGC) and retinal pigmented epithelium (RPE) cells. Bioactive sphingolipids, as sphingosine-1- phosphate (S1P) and ceramide-1-phosphate (C1P), are established mediators of inflammation and fibrosis and we have shown that S1P stimulates MGC migration (Simon et al; 2015). We now analyzed if they promote RPE migration. We supplemented ARPE19 cells, a human RPE cell line, with 5 μM S1P or 10 μM C1P. We pretreated them with SphkI2 or NVP, inhibitors of sphingosine kinase-1 (SphK1) and ceramide kinase (CerK), respectively to analyze if endogenous S1P or C1P stimulate cell migration, and with W146 and BML241, S1P1 and S1P3 antagonists, respectively to investigate if S1P activated these receptors. Migration was analyzed by the scratch wound assay. Exogenous S1P or C1P significantly promoted RPE cell migration, but their combined addition had no additive effect. Inhibiting S1P synthesis significantly reduced cell migration, and exogenous S1P and C1P partially restored it. In contrast, NVP treatment had no effect on RPE migration. Pretreatment with W146 reduced RPE migration both in control and S1P- supplemented cultures, while BML241 only reduced it in S1P- treated cultures. Our results suggest that endogenous synthesis of S1P activates S1P1 to induce RPE cell migration whereas exogenous S1P stimulates migration by activating both S1P1 and S1P3. Notably, exogenous C1P enhances RPE cell migration but its endogenous synthesis does not. Noteworthy, when added together, S1P and C1P had the same effect on migration as when added separately, implying they may share common signaling pathways. Hence, sphingolipids appear as central regulators of cell migration, and targeting their metabolism might provide tools for treating proliferative retinopathies.
Fil: Simon, Maria Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Vera, Marcela Sonia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Rotstein, Nora Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Reunión Anual de Sociedades de Biociencia 2019; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); XXI Reunión Anual de la Sociedad Argentina de Biología (SAB); XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP); IX Reunión Anual de la Asociación Argentina de Nanomedicinas (NANOMED-ar); VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACyTAL)
Mar del Plata, Buenos Aires
Argentina
Sociedad Argentina de Investigación Clínica
Asociación Argentina de Farmacología Experimental
Sociedad Argentina de Biología
Sociedad Argentina de Protozoología
Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
The Histochemical Society
description Retinal proliferative diseases, frequent causes of vision loss, involve excessive migration and proliferation of Müller glial cells (MGC) and retinal pigmented epithelium (RPE) cells. Bioactive sphingolipids, as sphingosine-1- phosphate (S1P) and ceramide-1-phosphate (C1P), are established mediators of inflammation and fibrosis and we have shown that S1P stimulates MGC migration (Simon et al; 2015). We now analyzed if they promote RPE migration. We supplemented ARPE19 cells, a human RPE cell line, with 5 μM S1P or 10 μM C1P. We pretreated them with SphkI2 or NVP, inhibitors of sphingosine kinase-1 (SphK1) and ceramide kinase (CerK), respectively to analyze if endogenous S1P or C1P stimulate cell migration, and with W146 and BML241, S1P1 and S1P3 antagonists, respectively to investigate if S1P activated these receptors. Migration was analyzed by the scratch wound assay. Exogenous S1P or C1P significantly promoted RPE cell migration, but their combined addition had no additive effect. Inhibiting S1P synthesis significantly reduced cell migration, and exogenous S1P and C1P partially restored it. In contrast, NVP treatment had no effect on RPE migration. Pretreatment with W146 reduced RPE migration both in control and S1P- supplemented cultures, while BML241 only reduced it in S1P- treated cultures. Our results suggest that endogenous synthesis of S1P activates S1P1 to induce RPE cell migration whereas exogenous S1P stimulates migration by activating both S1P1 and S1P3. Notably, exogenous C1P enhances RPE cell migration but its endogenous synthesis does not. Noteworthy, when added together, S1P and C1P had the same effect on migration as when added separately, implying they may share common signaling pathways. Hence, sphingolipids appear as central regulators of cell migration, and targeting their metabolism might provide tools for treating proliferative retinopathies.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
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Journal
http://purl.org/coar/resource_type/c_5794
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status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/188866
Recruiting sphingolipids to promote migration of retinal pigment epithelium cells; Reunión Anual de Sociedades de Biociencia 2019; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); XXI Reunión Anual de la Sociedad Argentina de Biología (SAB); XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP); IX Reunión Anual de la Asociación Argentina de Nanomedicinas (NANOMED-ar); VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACyTAL); Mar del Plata, Buenos Aires; Argentina; 2019; 176-177
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/188866
identifier_str_mv Recruiting sphingolipids to promote migration of retinal pigment epithelium cells; Reunión Anual de Sociedades de Biociencia 2019; LXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); LI Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); XXI Reunión Anual de la Sociedad Argentina de Biología (SAB); XXXI Reunión Anual de la Sociedad Argentina de Protozoología (SAP); IX Reunión Anual de la Asociación Argentina de Nanomedicinas (NANOMED-ar); VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACyTAL); Mar del Plata, Buenos Aires; Argentina; 2019; 176-177
0025-7680
1669-9106
CONICET Digital
CONICET
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language eng
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dc.publisher.none.fl_str_mv Medicina (Buenos Aires)
publisher.none.fl_str_mv Medicina (Buenos Aires)
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