p75NTR and its ligand proNGF activate paracrine mechanisms etiological to the vascular, inflammatory, and neurodegenerative pathologies of diabetic retinopathy

Autores
Barcelona, Pablo Federico; Sitaras, Nicholas; Galan, Alba; Esquiva, Gema; Jmaeff, Sean; Jian, Yiman; Sarunic, Marinko V.; Cuenca, Nicolas; Sapieha, Przemyslaw; Saragovi, H. Uri
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In many diseases, expression and ligand-dependent activity of the p75NTR receptor can promote pericyte and vascular dysfunction, inflammation, glial activation, and neurodegeneration. Diabetic retinopathy (DR) is characterized by all of these pathological events. However, the mechanisms by which p75NTR may be implicated at each stage of DR pathology remain poorly understood. Here, in a streptozotocin mouse model of diabetic retinopathy, we report that p75NTR is up-regulated very early in glia and in pericytes to mediate ligand-dependent induction of inflammatory cytokines, disruption of the neuro-glia-vascular unit, promotion of blood-retina-barrier breakdown, edema, and neuronal death. In a mouse model of oxygen-induced retinopathy, mimicking proliferative DR, p75NTR?dependent inflammation leads to ischemia and pathological angiogenesis through Semaphorin 3A. The acute use of antagonists of p75NTR or antagonists of the ligand proNGF suppresses each distinct phase of pathology, ameliorate disease, and prevent disease progression. Thus, our study documents novel disease mechanisms, and validates druggable targets for diabetic retinopathy.
Fil: Barcelona, Pablo Federico. Mc Gill University. Lady Davis Research Intitute; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Sitaras, Nicholas. University of Montreal; Canadá
Fil: Galan, Alba. Mc Gill University. Lady Davis Research Intitute; Canadá
Fil: Esquiva, Gema. Universidad de Alicante; España
Fil: Jmaeff, Sean. Mc Gill University. Lady Davis Research Intitute; Canadá
Fil: Jian, Yiman. University Fraser Simon; Canadá
Fil: Sarunic, Marinko V.. University Fraser Simon; Canadá
Fil: Cuenca, Nicolas. Universidad de Alicante. Facultad de Ciencias; España
Fil: Sapieha, Przemyslaw. University of Montreal; Canadá
Fil: Saragovi, H. Uri. Mc Gill University. Lady Davis Research Intitute; Canadá
Materia
P75 NTR
ALFA2M
DIABETES
PRONGF
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:11336/48048
Acceder
id CONICETDig_ce22314ff6174784c538d628558258c9
oai_identifier_str oai:ri.conicet.gov.ar:11336/48048
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling p75NTR and its ligand proNGF activate paracrine mechanisms etiological to the vascular, inflammatory, and neurodegenerative pathologies of diabetic retinopathyBarcelona, Pablo FedericoSitaras, NicholasGalan, AlbaEsquiva, GemaJmaeff, SeanJian, YimanSarunic, Marinko V.Cuenca, NicolasSapieha, PrzemyslawSaragovi, H. UriP75 NTRALFA2MDIABETESPRONGFhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1In many diseases, expression and ligand-dependent activity of the p75NTR receptor can promote pericyte and vascular dysfunction, inflammation, glial activation, and neurodegeneration. Diabetic retinopathy (DR) is characterized by all of these pathological events. However, the mechanisms by which p75NTR may be implicated at each stage of DR pathology remain poorly understood. Here, in a streptozotocin mouse model of diabetic retinopathy, we report that p75NTR is up-regulated very early in glia and in pericytes to mediate ligand-dependent induction of inflammatory cytokines, disruption of the neuro-glia-vascular unit, promotion of blood-retina-barrier breakdown, edema, and neuronal death. In a mouse model of oxygen-induced retinopathy, mimicking proliferative DR, p75NTR?dependent inflammation leads to ischemia and pathological angiogenesis through Semaphorin 3A. The acute use of antagonists of p75NTR or antagonists of the ligand proNGF suppresses each distinct phase of pathology, ameliorate disease, and prevent disease progression. Thus, our study documents novel disease mechanisms, and validates druggable targets for diabetic retinopathy.Fil: Barcelona, Pablo Federico. Mc Gill University. Lady Davis Research Intitute; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Sitaras, Nicholas. University of Montreal; CanadáFil: Galan, Alba. Mc Gill University. Lady Davis Research Intitute; CanadáFil: Esquiva, Gema. Universidad de Alicante; EspañaFil: Jmaeff, Sean. Mc Gill University. Lady Davis Research Intitute; CanadáFil: Jian, Yiman. University Fraser Simon; CanadáFil: Sarunic, Marinko V.. University Fraser Simon; CanadáFil: Cuenca, Nicolas. Universidad de Alicante. Facultad de Ciencias; EspañaFil: Sapieha, Przemyslaw. University of Montreal; CanadáFil: Saragovi, H. Uri. Mc Gill University. Lady Davis Research Intitute; CanadáSociety for Neuroscience2016-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/48048Barcelona, Pablo Federico; Sitaras, Nicholas; Galan, Alba; Esquiva, Gema; Jmaeff, Sean; et al.; p75NTR and its ligand proNGF activate paracrine mechanisms etiological to the vascular, inflammatory, and neurodegenerative pathologies of diabetic retinopathy; Society for Neuroscience; Journal of Neuroscience; 36; 34; 8-2016; 8826-88410270-64741529-2401CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.jneurosci.org/content/36/34/8826info:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.4278-15.2016info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:38:04Zoai:ri.conicet.gov.ar:11336/48048instacron: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 09:38:04.334CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv p75NTR and its ligand proNGF activate paracrine mechanisms etiological to the vascular, inflammatory, and neurodegenerative pathologies of diabetic retinopathy
title p75NTR and its ligand proNGF activate paracrine mechanisms etiological to the vascular, inflammatory, and neurodegenerative pathologies of diabetic retinopathy
spellingShingle p75NTR and its ligand proNGF activate paracrine mechanisms etiological to the vascular, inflammatory, and neurodegenerative pathologies of diabetic retinopathy
Barcelona, Pablo Federico
P75 NTR
ALFA2M
DIABETES
PRONGF
title_short p75NTR and its ligand proNGF activate paracrine mechanisms etiological to the vascular, inflammatory, and neurodegenerative pathologies of diabetic retinopathy
title_full p75NTR and its ligand proNGF activate paracrine mechanisms etiological to the vascular, inflammatory, and neurodegenerative pathologies of diabetic retinopathy
title_fullStr p75NTR and its ligand proNGF activate paracrine mechanisms etiological to the vascular, inflammatory, and neurodegenerative pathologies of diabetic retinopathy
title_full_unstemmed p75NTR and its ligand proNGF activate paracrine mechanisms etiological to the vascular, inflammatory, and neurodegenerative pathologies of diabetic retinopathy
title_sort p75NTR and its ligand proNGF activate paracrine mechanisms etiological to the vascular, inflammatory, and neurodegenerative pathologies of diabetic retinopathy
dc.creator.none.fl_str_mv Barcelona, Pablo Federico
Sitaras, Nicholas
Galan, Alba
Esquiva, Gema
Jmaeff, Sean
Jian, Yiman
Sarunic, Marinko V.
Cuenca, Nicolas
Sapieha, Przemyslaw
Saragovi, H. Uri
author Barcelona, Pablo Federico
author_facet Barcelona, Pablo Federico
Sitaras, Nicholas
Galan, Alba
Esquiva, Gema
Jmaeff, Sean
Jian, Yiman
Sarunic, Marinko V.
Cuenca, Nicolas
Sapieha, Przemyslaw
Saragovi, H. Uri
author_role author
author2 Sitaras, Nicholas
Galan, Alba
Esquiva, Gema
Jmaeff, Sean
Jian, Yiman
Sarunic, Marinko V.
Cuenca, Nicolas
Sapieha, Przemyslaw
Saragovi, H. Uri
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv P75 NTR
ALFA2M
DIABETES
PRONGF
topic P75 NTR
ALFA2M
DIABETES
PRONGF
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In many diseases, expression and ligand-dependent activity of the p75NTR receptor can promote pericyte and vascular dysfunction, inflammation, glial activation, and neurodegeneration. Diabetic retinopathy (DR) is characterized by all of these pathological events. However, the mechanisms by which p75NTR may be implicated at each stage of DR pathology remain poorly understood. Here, in a streptozotocin mouse model of diabetic retinopathy, we report that p75NTR is up-regulated very early in glia and in pericytes to mediate ligand-dependent induction of inflammatory cytokines, disruption of the neuro-glia-vascular unit, promotion of blood-retina-barrier breakdown, edema, and neuronal death. In a mouse model of oxygen-induced retinopathy, mimicking proliferative DR, p75NTR?dependent inflammation leads to ischemia and pathological angiogenesis through Semaphorin 3A. The acute use of antagonists of p75NTR or antagonists of the ligand proNGF suppresses each distinct phase of pathology, ameliorate disease, and prevent disease progression. Thus, our study documents novel disease mechanisms, and validates druggable targets for diabetic retinopathy.
Fil: Barcelona, Pablo Federico. Mc Gill University. Lady Davis Research Intitute; Canadá. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Sitaras, Nicholas. University of Montreal; Canadá
Fil: Galan, Alba. Mc Gill University. Lady Davis Research Intitute; Canadá
Fil: Esquiva, Gema. Universidad de Alicante; España
Fil: Jmaeff, Sean. Mc Gill University. Lady Davis Research Intitute; Canadá
Fil: Jian, Yiman. University Fraser Simon; Canadá
Fil: Sarunic, Marinko V.. University Fraser Simon; Canadá
Fil: Cuenca, Nicolas. Universidad de Alicante. Facultad de Ciencias; España
Fil: Sapieha, Przemyslaw. University of Montreal; Canadá
Fil: Saragovi, H. Uri. Mc Gill University. Lady Davis Research Intitute; Canadá
description In many diseases, expression and ligand-dependent activity of the p75NTR receptor can promote pericyte and vascular dysfunction, inflammation, glial activation, and neurodegeneration. Diabetic retinopathy (DR) is characterized by all of these pathological events. However, the mechanisms by which p75NTR may be implicated at each stage of DR pathology remain poorly understood. Here, in a streptozotocin mouse model of diabetic retinopathy, we report that p75NTR is up-regulated very early in glia and in pericytes to mediate ligand-dependent induction of inflammatory cytokines, disruption of the neuro-glia-vascular unit, promotion of blood-retina-barrier breakdown, edema, and neuronal death. In a mouse model of oxygen-induced retinopathy, mimicking proliferative DR, p75NTR?dependent inflammation leads to ischemia and pathological angiogenesis through Semaphorin 3A. The acute use of antagonists of p75NTR or antagonists of the ligand proNGF suppresses each distinct phase of pathology, ameliorate disease, and prevent disease progression. Thus, our study documents novel disease mechanisms, and validates druggable targets for diabetic retinopathy.
publishDate 2016
dc.date.none.fl_str_mv 2016-08
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/11336/48048
Barcelona, Pablo Federico; Sitaras, Nicholas; Galan, Alba; Esquiva, Gema; Jmaeff, Sean; et al.; p75NTR and its ligand proNGF activate paracrine mechanisms etiological to the vascular, inflammatory, and neurodegenerative pathologies of diabetic retinopathy; Society for Neuroscience; Journal of Neuroscience; 36; 34; 8-2016; 8826-8841
0270-6474
1529-2401
CONICET Digital
CONICET
url http://hdl.handle.net/11336/48048
identifier_str_mv Barcelona, Pablo Federico; Sitaras, Nicholas; Galan, Alba; Esquiva, Gema; Jmaeff, Sean; et al.; p75NTR and its ligand proNGF activate paracrine mechanisms etiological to the vascular, inflammatory, and neurodegenerative pathologies of diabetic retinopathy; Society for Neuroscience; Journal of Neuroscience; 36; 34; 8-2016; 8826-8841
0270-6474
1529-2401
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.jneurosci.org/content/36/34/8826
info:eu-repo/semantics/altIdentifier/doi/10.1523/JNEUROSCI.4278-15.2016
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
dc.publisher.none.fl_str_mv Society for Neuroscience
publisher.none.fl_str_mv Society for Neuroscience
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
_version_ 1844613201991303168
score 13.070432

Publicaciones similares