The SphK1/S1P axis regulates morphology and cell-cell interactions of retina pigment epithelium cells

Autores
Torlaschi, Camila; Gutierrez Jofré, Gabriela Mabel; Rotstein, Nora Patricia; Simón, M. Victoria
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Sphingosine-1-phosphate (S1P), a bioactive sphingolipid, regulates multiple key cellularprocesses. We demonstrated that S1P promotes migration and proinflammatory cytokine releasein retinal pigment epithelium (RPE) cells. These cells provide the retina with a physical andmetabolic barrier, the disruption of which contributes to the onset of numerous retinopathies.We now investigated whether S1P controlled RPE morphology and cell-cell interactions. Treatmentof human RPE cell line (ARPE-19) cultures with PF543, a sphingosine kinase-1 (SphK1) inhibitor,decreased cell migration in confluent cultures. In sub-confluent cultures, PF543 inducedcell retraction and the occurrence of elongated, spindle-like cells, absent in controls. PF543 inducedsimilar morphological changes in D407 RPE cell line. S1P preserved cell morphology inPF543-treated cultures, reducing the presence of spindle-like cells. Clusters of paxillin and talin,focal adhesion components, virtually disappeared from cell periphery in PF543-treated cells butwere preserved upon S1P addition. While PF543 decreased fibronectin expression and promotedZO-1 delocalization from the cell membranes, S1P prevented these changes. Pretreatment withW146 and JTE013, S1P1 and S1P2 antagonists, respectively, before adding PF543 and S1P, partiallyblocked S1P preservation of cell morphology, whereas incubation with BML-241, a S1P3antagonist, had no effect, implying that activation of S1P1 and S1P2 was required for S1P effect.In control cells, morphology was not affected either by the addition of S1P1, S1P2 and S1P3 antagonistsor by inhibiting the export of S1P with an inhibitor for Spinster-2, its major transporter,suggesting that endogenous S1P preservation of morphology did not involve ?inside-out?signaling. Our results suggest that SphK1 activity and exogenous S1P were required for controllingRPE cytoskeletal changes and cell interactions, essential for preserving its barrier function.
Fil: Torlaschi, Camila. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Gutierrez Jofré, Gabriela Mabel. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Simón, M. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Materia
SPHINGOSINE-1-PHOSPHATE
SPHINGOSINE KINASE 1
CELL MORPHOLOGY
CELL ADHESION
RETINAL PIGMENT EPITHELIUM
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:11336/277580
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/277580
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The SphK1/S1P axis regulates morphology and cell-cell interactions of retina pigment epithelium cellsTorlaschi, CamilaGutierrez Jofré, Gabriela MabelRotstein, Nora PatriciaSimón, M. VictoriaSPHINGOSINE-1-PHOSPHATESPHINGOSINE KINASE 1CELL MORPHOLOGYCELL ADHESIONRETINAL PIGMENT EPITHELIUMhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Sphingosine-1-phosphate (S1P), a bioactive sphingolipid, regulates multiple key cellularprocesses. We demonstrated that S1P promotes migration and proinflammatory cytokine releasein retinal pigment epithelium (RPE) cells. These cells provide the retina with a physical andmetabolic barrier, the disruption of which contributes to the onset of numerous retinopathies.We now investigated whether S1P controlled RPE morphology and cell-cell interactions. Treatmentof human RPE cell line (ARPE-19) cultures with PF543, a sphingosine kinase-1 (SphK1) inhibitor,decreased cell migration in confluent cultures. In sub-confluent cultures, PF543 inducedcell retraction and the occurrence of elongated, spindle-like cells, absent in controls. PF543 inducedsimilar morphological changes in D407 RPE cell line. S1P preserved cell morphology inPF543-treated cultures, reducing the presence of spindle-like cells. Clusters of paxillin and talin,focal adhesion components, virtually disappeared from cell periphery in PF543-treated cells butwere preserved upon S1P addition. While PF543 decreased fibronectin expression and promotedZO-1 delocalization from the cell membranes, S1P prevented these changes. Pretreatment withW146 and JTE013, S1P1 and S1P2 antagonists, respectively, before adding PF543 and S1P, partiallyblocked S1P preservation of cell morphology, whereas incubation with BML-241, a S1P3antagonist, had no effect, implying that activation of S1P1 and S1P2 was required for S1P effect.In control cells, morphology was not affected either by the addition of S1P1, S1P2 and S1P3 antagonistsor by inhibiting the export of S1P with an inhibitor for Spinster-2, its major transporter,suggesting that endogenous S1P preservation of morphology did not involve ?inside-out?signaling. Our results suggest that SphK1 activity and exogenous S1P were required for controllingRPE cytoskeletal changes and cell interactions, essential for preserving its barrier function.Fil: Torlaschi, Camila. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Gutierrez Jofré, Gabriela Mabel. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. 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; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Simón, M. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaCell Press2025-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/277580Torlaschi, Camila; Gutierrez Jofré, Gabriela Mabel; Rotstein, Nora Patricia; Simón, M. Victoria; The SphK1/S1P axis regulates morphology and cell-cell interactions of retina pigment epithelium cells; Cell Press; Heliyon; 11; 14; 8-2025; 1-172405-84402405-8440CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2405844025021401info:eu-repo/semantics/altIdentifier/doi/10.1016/j.heliyon.2025.e43749info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-17T15:42:14Zoai:ri.conicet.gov.ar:11336/277580instacron: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:34982025-12-17 15:42:15.229CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The SphK1/S1P axis regulates morphology and cell-cell interactions of retina pigment epithelium cells
title The SphK1/S1P axis regulates morphology and cell-cell interactions of retina pigment epithelium cells
spellingShingle The SphK1/S1P axis regulates morphology and cell-cell interactions of retina pigment epithelium cells
Torlaschi, Camila
SPHINGOSINE-1-PHOSPHATE
SPHINGOSINE KINASE 1
CELL MORPHOLOGY
CELL ADHESION
RETINAL PIGMENT EPITHELIUM
title_short The SphK1/S1P axis regulates morphology and cell-cell interactions of retina pigment epithelium cells
title_full The SphK1/S1P axis regulates morphology and cell-cell interactions of retina pigment epithelium cells
title_fullStr The SphK1/S1P axis regulates morphology and cell-cell interactions of retina pigment epithelium cells
title_full_unstemmed The SphK1/S1P axis regulates morphology and cell-cell interactions of retina pigment epithelium cells
title_sort The SphK1/S1P axis regulates morphology and cell-cell interactions of retina pigment epithelium cells
dc.creator.none.fl_str_mv Torlaschi, Camila
Gutierrez Jofré, Gabriela Mabel
Rotstein, Nora Patricia
Simón, M. Victoria
author Torlaschi, Camila
author_facet Torlaschi, Camila
Gutierrez Jofré, Gabriela Mabel
Rotstein, Nora Patricia
Simón, M. Victoria
author_role author
author2 Gutierrez Jofré, Gabriela Mabel
Rotstein, Nora Patricia
Simón, M. Victoria
author2_role author
author
author
dc.subject.none.fl_str_mv SPHINGOSINE-1-PHOSPHATE
SPHINGOSINE KINASE 1
CELL MORPHOLOGY
CELL ADHESION
RETINAL PIGMENT EPITHELIUM
topic SPHINGOSINE-1-PHOSPHATE
SPHINGOSINE KINASE 1
CELL MORPHOLOGY
CELL ADHESION
RETINAL PIGMENT EPITHELIUM
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Sphingosine-1-phosphate (S1P), a bioactive sphingolipid, regulates multiple key cellularprocesses. We demonstrated that S1P promotes migration and proinflammatory cytokine releasein retinal pigment epithelium (RPE) cells. These cells provide the retina with a physical andmetabolic barrier, the disruption of which contributes to the onset of numerous retinopathies.We now investigated whether S1P controlled RPE morphology and cell-cell interactions. Treatmentof human RPE cell line (ARPE-19) cultures with PF543, a sphingosine kinase-1 (SphK1) inhibitor,decreased cell migration in confluent cultures. In sub-confluent cultures, PF543 inducedcell retraction and the occurrence of elongated, spindle-like cells, absent in controls. PF543 inducedsimilar morphological changes in D407 RPE cell line. S1P preserved cell morphology inPF543-treated cultures, reducing the presence of spindle-like cells. Clusters of paxillin and talin,focal adhesion components, virtually disappeared from cell periphery in PF543-treated cells butwere preserved upon S1P addition. While PF543 decreased fibronectin expression and promotedZO-1 delocalization from the cell membranes, S1P prevented these changes. Pretreatment withW146 and JTE013, S1P1 and S1P2 antagonists, respectively, before adding PF543 and S1P, partiallyblocked S1P preservation of cell morphology, whereas incubation with BML-241, a S1P3antagonist, had no effect, implying that activation of S1P1 and S1P2 was required for S1P effect.In control cells, morphology was not affected either by the addition of S1P1, S1P2 and S1P3 antagonistsor by inhibiting the export of S1P with an inhibitor for Spinster-2, its major transporter,suggesting that endogenous S1P preservation of morphology did not involve ?inside-out?signaling. Our results suggest that SphK1 activity and exogenous S1P were required for controllingRPE cytoskeletal changes and cell interactions, essential for preserving its barrier function.
Fil: Torlaschi, Camila. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Gutierrez Jofré, Gabriela Mabel. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
Fil: Simón, M. 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. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
description Sphingosine-1-phosphate (S1P), a bioactive sphingolipid, regulates multiple key cellularprocesses. We demonstrated that S1P promotes migration and proinflammatory cytokine releasein retinal pigment epithelium (RPE) cells. These cells provide the retina with a physical andmetabolic barrier, the disruption of which contributes to the onset of numerous retinopathies.We now investigated whether S1P controlled RPE morphology and cell-cell interactions. Treatmentof human RPE cell line (ARPE-19) cultures with PF543, a sphingosine kinase-1 (SphK1) inhibitor,decreased cell migration in confluent cultures. In sub-confluent cultures, PF543 inducedcell retraction and the occurrence of elongated, spindle-like cells, absent in controls. PF543 inducedsimilar morphological changes in D407 RPE cell line. S1P preserved cell morphology inPF543-treated cultures, reducing the presence of spindle-like cells. Clusters of paxillin and talin,focal adhesion components, virtually disappeared from cell periphery in PF543-treated cells butwere preserved upon S1P addition. While PF543 decreased fibronectin expression and promotedZO-1 delocalization from the cell membranes, S1P prevented these changes. Pretreatment withW146 and JTE013, S1P1 and S1P2 antagonists, respectively, before adding PF543 and S1P, partiallyblocked S1P preservation of cell morphology, whereas incubation with BML-241, a S1P3antagonist, had no effect, implying that activation of S1P1 and S1P2 was required for S1P effect.In control cells, morphology was not affected either by the addition of S1P1, S1P2 and S1P3 antagonistsor by inhibiting the export of S1P with an inhibitor for Spinster-2, its major transporter,suggesting that endogenous S1P preservation of morphology did not involve ?inside-out?signaling. Our results suggest that SphK1 activity and exogenous S1P were required for controllingRPE cytoskeletal changes and cell interactions, essential for preserving its barrier function.
publishDate 2025
dc.date.none.fl_str_mv 2025-08
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/11336/277580
Torlaschi, Camila; Gutierrez Jofré, Gabriela Mabel; Rotstein, Nora Patricia; Simón, M. Victoria; The SphK1/S1P axis regulates morphology and cell-cell interactions of retina pigment epithelium cells; Cell Press; Heliyon; 11; 14; 8-2025; 1-17
2405-8440
2405-8440
CONICET Digital
CONICET
url http://hdl.handle.net/11336/277580
identifier_str_mv Torlaschi, Camila; Gutierrez Jofré, Gabriela Mabel; Rotstein, Nora Patricia; Simón, M. Victoria; The SphK1/S1P axis regulates morphology and cell-cell interactions of retina pigment epithelium cells; Cell Press; Heliyon; 11; 14; 8-2025; 1-17
2405-8440
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S2405844025021401
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.heliyon.2025.e43749
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Cell Press
publisher.none.fl_str_mv Cell Press
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 13.176297

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