Sphingosine-1-phosphate: Potential mediator in retinal proliferative disorders?

Autores
Simon, Maria Victoria; Torlaschi, Camila; Gutierrez Jofré, Gabriela Mabel; Rotstein, Nora Patricia
Año de publicación
2024
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Introduction Fibrosis is a common feature of retina proliferative diseases, as diabetic retinopathy and proliferative vitreoretinopathy, which lead to vision loss. Dysregulation of cell attachment, migration and de-differentiation of Müller glial cells (MGC) and retinal pigment epithelium (RPE) cells, which provide structural and metabolic support in the retina contribute to the fibrotic process. Modulation of this process might hold the key to prevent the development of proliferative retinopaties. Sphingolipids such as sphingosine-1- phosphate (S1P), which regulates critical cellular functions, like proliferation, inflammation, migration, survival and differentiation, advance fibrosis in different tissues, but their role in the retina is still unclear. Objectives To study the role of S1P in the regulation of processes leading to fibrosis in the retina. Methods Primary MGC cultures and RPE cell line cultures (ARPE-19 and D407) were exposed to 5 uM S1P for 24 h. We incubated cell cultures with sphingosine kinase inhibitors SphKI2 and PF-543, to study the role of endogenous S1P, with W146, JTE-013 and BML241, specific S1P1, S1P2 and S1P3 antagonists, respectively, to analyze the involvement of S1P receptors . The ERK/MAPK and PI3K signaling pathways were analyzed with specific inhibitors U0126 and Ly294002, respectively. Cell migration was de- termined by the scratch wound assay, RPE cell morphology and localization of adherent proteins were analyzed by immunocyto- chemistry, pro-inflammatory cytokines were evaluated by PCR. Results We demonstrated that MGC synthesize S1P, which signals through S1P3 and the PI3K and ERK/MAPK pathways to induce gli- al migration. S1P also stimulated RPE cell migration and this effect required endogenous synthesis of S1P. S1P increased the transcription of pro-inflammatory cytokines IL-6 and IL-8, and of epithelial to mesenchymal transition (EMT) marker α-smooth muscle actin (α-SMA) in RPE cells. Blocking S1P syntesis led to RPE cell retraction, and to the disassembly of focal adhesions and cell-cell contacts. Exogenous S1P prevented these changes, signalling through S1P1 and S1P2. Conclusion Our results showed that S1P promoted MGC and RPE cell migration, and RPE release of pro-inflammatory cytokines, which might contribute to retinal fibrosis. However, they also imply that endogenous S1P regulates RPE proper attachment to neighboring cells and to the extracellular matrix, thus preserving monolayer integrity. This suggests a dual role for S1P in the retina, either protective or deletereous. Uncovering the molecular cues that modulate these S1P effects might provide new tools for treating retina proliferative disorders.
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: 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
Fil: Gutierrez Jofré, Gabriela Mabel. 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
XXVI Biennial Meeting of the International Society for Eye Research
Buenos Aires
Argentina
International Society for Eye Research
Materia
RETINAL PIGMENT EPITHELIUM
MÜLLER GLIAL CELLS
SPHINGOSINE-1- PHOSPHATE
RETINA
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:11336/253040
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/253040
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Sphingosine-1-phosphate: Potential mediator in retinal proliferative disorders?Simon, Maria VictoriaTorlaschi, CamilaGutierrez Jofré, Gabriela MabelRotstein, Nora PatriciaRETINAL PIGMENT EPITHELIUMMÜLLER GLIAL CELLSSPHINGOSINE-1- PHOSPHATERETINAhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Introduction Fibrosis is a common feature of retina proliferative diseases, as diabetic retinopathy and proliferative vitreoretinopathy, which lead to vision loss. Dysregulation of cell attachment, migration and de-differentiation of Müller glial cells (MGC) and retinal pigment epithelium (RPE) cells, which provide structural and metabolic support in the retina contribute to the fibrotic process. Modulation of this process might hold the key to prevent the development of proliferative retinopaties. Sphingolipids such as sphingosine-1- phosphate (S1P), which regulates critical cellular functions, like proliferation, inflammation, migration, survival and differentiation, advance fibrosis in different tissues, but their role in the retina is still unclear. Objectives To study the role of S1P in the regulation of processes leading to fibrosis in the retina. Methods Primary MGC cultures and RPE cell line cultures (ARPE-19 and D407) were exposed to 5 uM S1P for 24 h. We incubated cell cultures with sphingosine kinase inhibitors SphKI2 and PF-543, to study the role of endogenous S1P, with W146, JTE-013 and BML241, specific S1P1, S1P2 and S1P3 antagonists, respectively, to analyze the involvement of S1P receptors . The ERK/MAPK and PI3K signaling pathways were analyzed with specific inhibitors U0126 and Ly294002, respectively. Cell migration was de- termined by the scratch wound assay, RPE cell morphology and localization of adherent proteins were analyzed by immunocyto- chemistry, pro-inflammatory cytokines were evaluated by PCR. Results We demonstrated that MGC synthesize S1P, which signals through S1P3 and the PI3K and ERK/MAPK pathways to induce gli- al migration. S1P also stimulated RPE cell migration and this effect required endogenous synthesis of S1P. S1P increased the transcription of pro-inflammatory cytokines IL-6 and IL-8, and of epithelial to mesenchymal transition (EMT) marker α-smooth muscle actin (α-SMA) in RPE cells. Blocking S1P syntesis led to RPE cell retraction, and to the disassembly of focal adhesions and cell-cell contacts. Exogenous S1P prevented these changes, signalling through S1P1 and S1P2. Conclusion Our results showed that S1P promoted MGC and RPE cell migration, and RPE release of pro-inflammatory cytokines, which might contribute to retinal fibrosis. However, they also imply that endogenous S1P regulates RPE proper attachment to neighboring cells and to the extracellular matrix, thus preserving monolayer integrity. This suggests a dual role for S1P in the retina, either protective or deletereous. Uncovering the molecular cues that modulate these S1P effects might provide new tools for treating retina proliferative disorders.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: 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; ArgentinaFil: Gutierrez Jofré, Gabriela Mabel. 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; ArgentinaXXVI Biennial Meeting of the International Society for Eye ResearchBuenos AiresArgentinaInternational Society for Eye ResearchInternational Society for Eye Research2024info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectEncuentroBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/253040Sphingosine-1-phosphate: Potential mediator in retinal proliferative disorders?; XXVI Biennial Meeting of the International Society for Eye Research; Buenos Aires; Argentina; 2024; 317-318CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://iserbiennialmeeting2024.org/abstract-book/Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T10:42:08Zoai:ri.conicet.gov.ar:11336/253040instacron: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:34982025-09-17 10:42:09.056CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Sphingosine-1-phosphate: Potential mediator in retinal proliferative disorders?
title Sphingosine-1-phosphate: Potential mediator in retinal proliferative disorders?
spellingShingle Sphingosine-1-phosphate: Potential mediator in retinal proliferative disorders?
Simon, Maria Victoria
RETINAL PIGMENT EPITHELIUM
MÜLLER GLIAL CELLS
SPHINGOSINE-1- PHOSPHATE
RETINA
title_short Sphingosine-1-phosphate: Potential mediator in retinal proliferative disorders?
title_full Sphingosine-1-phosphate: Potential mediator in retinal proliferative disorders?
title_fullStr Sphingosine-1-phosphate: Potential mediator in retinal proliferative disorders?
title_full_unstemmed Sphingosine-1-phosphate: Potential mediator in retinal proliferative disorders?
title_sort Sphingosine-1-phosphate: Potential mediator in retinal proliferative disorders?
dc.creator.none.fl_str_mv Simon, Maria Victoria
Torlaschi, Camila
Gutierrez Jofré, Gabriela Mabel
Rotstein, Nora Patricia
author Simon, Maria Victoria
author_facet Simon, Maria Victoria
Torlaschi, Camila
Gutierrez Jofré, Gabriela Mabel
Rotstein, Nora Patricia
author_role author
author2 Torlaschi, Camila
Gutierrez Jofré, Gabriela Mabel
Rotstein, Nora Patricia
author2_role author
author
author
dc.subject.none.fl_str_mv RETINAL PIGMENT EPITHELIUM
MÜLLER GLIAL CELLS
SPHINGOSINE-1- PHOSPHATE
RETINA
topic RETINAL PIGMENT EPITHELIUM
MÜLLER GLIAL CELLS
SPHINGOSINE-1- PHOSPHATE
RETINA
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Introduction Fibrosis is a common feature of retina proliferative diseases, as diabetic retinopathy and proliferative vitreoretinopathy, which lead to vision loss. Dysregulation of cell attachment, migration and de-differentiation of Müller glial cells (MGC) and retinal pigment epithelium (RPE) cells, which provide structural and metabolic support in the retina contribute to the fibrotic process. Modulation of this process might hold the key to prevent the development of proliferative retinopaties. Sphingolipids such as sphingosine-1- phosphate (S1P), which regulates critical cellular functions, like proliferation, inflammation, migration, survival and differentiation, advance fibrosis in different tissues, but their role in the retina is still unclear. Objectives To study the role of S1P in the regulation of processes leading to fibrosis in the retina. Methods Primary MGC cultures and RPE cell line cultures (ARPE-19 and D407) were exposed to 5 uM S1P for 24 h. We incubated cell cultures with sphingosine kinase inhibitors SphKI2 and PF-543, to study the role of endogenous S1P, with W146, JTE-013 and BML241, specific S1P1, S1P2 and S1P3 antagonists, respectively, to analyze the involvement of S1P receptors . The ERK/MAPK and PI3K signaling pathways were analyzed with specific inhibitors U0126 and Ly294002, respectively. Cell migration was de- termined by the scratch wound assay, RPE cell morphology and localization of adherent proteins were analyzed by immunocyto- chemistry, pro-inflammatory cytokines were evaluated by PCR. Results We demonstrated that MGC synthesize S1P, which signals through S1P3 and the PI3K and ERK/MAPK pathways to induce gli- al migration. S1P also stimulated RPE cell migration and this effect required endogenous synthesis of S1P. S1P increased the transcription of pro-inflammatory cytokines IL-6 and IL-8, and of epithelial to mesenchymal transition (EMT) marker α-smooth muscle actin (α-SMA) in RPE cells. Blocking S1P syntesis led to RPE cell retraction, and to the disassembly of focal adhesions and cell-cell contacts. Exogenous S1P prevented these changes, signalling through S1P1 and S1P2. Conclusion Our results showed that S1P promoted MGC and RPE cell migration, and RPE release of pro-inflammatory cytokines, which might contribute to retinal fibrosis. However, they also imply that endogenous S1P regulates RPE proper attachment to neighboring cells and to the extracellular matrix, thus preserving monolayer integrity. This suggests a dual role for S1P in the retina, either protective or deletereous. Uncovering the molecular cues that modulate these S1P effects might provide new tools for treating retina proliferative disorders.
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: 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
Fil: Gutierrez Jofré, Gabriela Mabel. 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
XXVI Biennial Meeting of the International Society for Eye Research
Buenos Aires
Argentina
International Society for Eye Research
description Introduction Fibrosis is a common feature of retina proliferative diseases, as diabetic retinopathy and proliferative vitreoretinopathy, which lead to vision loss. Dysregulation of cell attachment, migration and de-differentiation of Müller glial cells (MGC) and retinal pigment epithelium (RPE) cells, which provide structural and metabolic support in the retina contribute to the fibrotic process. Modulation of this process might hold the key to prevent the development of proliferative retinopaties. Sphingolipids such as sphingosine-1- phosphate (S1P), which regulates critical cellular functions, like proliferation, inflammation, migration, survival and differentiation, advance fibrosis in different tissues, but their role in the retina is still unclear. Objectives To study the role of S1P in the regulation of processes leading to fibrosis in the retina. Methods Primary MGC cultures and RPE cell line cultures (ARPE-19 and D407) were exposed to 5 uM S1P for 24 h. We incubated cell cultures with sphingosine kinase inhibitors SphKI2 and PF-543, to study the role of endogenous S1P, with W146, JTE-013 and BML241, specific S1P1, S1P2 and S1P3 antagonists, respectively, to analyze the involvement of S1P receptors . The ERK/MAPK and PI3K signaling pathways were analyzed with specific inhibitors U0126 and Ly294002, respectively. Cell migration was de- termined by the scratch wound assay, RPE cell morphology and localization of adherent proteins were analyzed by immunocyto- chemistry, pro-inflammatory cytokines were evaluated by PCR. Results We demonstrated that MGC synthesize S1P, which signals through S1P3 and the PI3K and ERK/MAPK pathways to induce gli- al migration. S1P also stimulated RPE cell migration and this effect required endogenous synthesis of S1P. S1P increased the transcription of pro-inflammatory cytokines IL-6 and IL-8, and of epithelial to mesenchymal transition (EMT) marker α-smooth muscle actin (α-SMA) in RPE cells. Blocking S1P syntesis led to RPE cell retraction, and to the disassembly of focal adhesions and cell-cell contacts. Exogenous S1P prevented these changes, signalling through S1P1 and S1P2. Conclusion Our results showed that S1P promoted MGC and RPE cell migration, and RPE release of pro-inflammatory cytokines, which might contribute to retinal fibrosis. However, they also imply that endogenous S1P regulates RPE proper attachment to neighboring cells and to the extracellular matrix, thus preserving monolayer integrity. This suggests a dual role for S1P in the retina, either protective or deletereous. Uncovering the molecular cues that modulate these S1P effects might provide new tools for treating retina proliferative disorders.
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Encuentro
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/253040
Sphingosine-1-phosphate: Potential mediator in retinal proliferative disorders?; XXVI Biennial Meeting of the International Society for Eye Research; Buenos Aires; Argentina; 2024; 317-318
CONICET Digital
CONICET
url http://hdl.handle.net/11336/253040
identifier_str_mv Sphingosine-1-phosphate: Potential mediator in retinal proliferative disorders?; XXVI Biennial Meeting of the International Society for Eye Research; Buenos Aires; Argentina; 2024; 317-318
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://iserbiennialmeeting2024.org/abstract-book/
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
dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv International Society for Eye Research
publisher.none.fl_str_mv International Society for Eye Research
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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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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