The non-canonical NOTCH ligand DLK1 exhibits a novel vascular role as a strong inhibitor of angiogenesis

El pdf es el manuscrito de autor.-- et al.

Detalles Bibliográficos
Autores: Rodríguez, Patricia, Higueras López, M. Ángeles, Fierro-Fernández, Marta, Monsalve, María, Rodríguez-Pascual, Fernando, Lamas Peláez, Santiago
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/75145
Acceso en línea:http://hdl.handle.net/10261/75145
Access Level:acceso abierto
Palabra clave:Angiogenesis
Delta-like 1
Pref-1
Endothelium
NOTCH
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spelling The non-canonical NOTCH ligand DLK1 exhibits a novel vascular role as a strong inhibitor of angiogenesisRodríguez, PatriciaHigueras López, M. ÁngelesFierro-Fernández, MartaMonsalve, MaríaRodríguez-Pascual, FernandoLamas Peláez, SantiagoAngiogenesisDelta-like 1Pref-1EndotheliumNOTCHEl pdf es el manuscrito de autor.-- et al.[Aims]: The epidermal growth factor-like protein Delta-like 1 (DLK1) regulates multiple differentiation processes. It resembles NOTCH ligands structurally and is considered a non-canonical ligand. Given the crucial role of the NOTCH pathway in angiogenesis, we hypothesized that DLK1 could regulate angiogenesis by interfering with NOTCH. We therefore investigated the expression and function of DLK1 in the vascular endothelium and its role in the regulation of angiogenesis.[Methods and Results]: We report DLK1 expression in the endothelium of different species, including human, cow, pig, and mouse. Angiogenesis was studied by using in vitro and in vivo models of angiotube formation in endothelial cells, retinal phenotypes in Dlk1-null mice, and vessel development in zebrafish. DLK1 overexpression strongly inhibited angiotube formation, whereas lung endothelial cells from Dlk1-null mice were highly angiogenic. In vivo studies demonstrated DLK1-mediated inhibition of neovessel formation and revealed an altered pattern of angiogenesis in the retinas of Dlk1-null mice. The expression of human DLK1 in zebrafish embryos severely altered the formation of intersegmental vessels, while knockdown of the orthologous gene was associated with ectopic and increased tumour-induced angiogenesis. NOTCH-dependent signalling as determined by gene expression reporters was inhibited by the presence of DLK1 in vascular endothelial cells. In contrast, Dlk1-null mice showed increased levels of NOTCH downstream targets, such as Snail and Slug.[Conclusion]: Our results unveil a novel inhibitory role for DLK1 in the regulation of angiogenesis, mediated by antagonism of the NOTCH pathway, and establish the basis for investigating its action in pathological settings.This work was supported by the conjoint grant Cardiovrep S2006/BIO-0194 from the Comunidad Autónoma de Madrid (to S.L., J.L.P., and J.M.R.), CSD 2007-00020 (to S.L. and M.M.), SAF2009-07520 (to S.L.), and BFU2007-61094 (to J.L.) all from the Spanish Ministerio de Ciencia e Innovación (MICINN).Peer reviewedOxford University PressComunidad de MadridMinisterio de Ciencia e Innovación (España)201320132011info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/75145reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#S2006/BIO-0194/CARDIOVREPhttp://dx.doi.org/10.1093/cvr/cvr296info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/751452026-05-22T06:33:51Z
dc.title.none.fl_str_mv The non-canonical NOTCH ligand DLK1 exhibits a novel vascular role as a strong inhibitor of angiogenesis
title The non-canonical NOTCH ligand DLK1 exhibits a novel vascular role as a strong inhibitor of angiogenesis
spellingShingle The non-canonical NOTCH ligand DLK1 exhibits a novel vascular role as a strong inhibitor of angiogenesis
Rodríguez, Patricia
Angiogenesis
Delta-like 1
Pref-1
Endothelium
NOTCH
title_short The non-canonical NOTCH ligand DLK1 exhibits a novel vascular role as a strong inhibitor of angiogenesis
title_full The non-canonical NOTCH ligand DLK1 exhibits a novel vascular role as a strong inhibitor of angiogenesis
title_fullStr The non-canonical NOTCH ligand DLK1 exhibits a novel vascular role as a strong inhibitor of angiogenesis
title_full_unstemmed The non-canonical NOTCH ligand DLK1 exhibits a novel vascular role as a strong inhibitor of angiogenesis
title_sort The non-canonical NOTCH ligand DLK1 exhibits a novel vascular role as a strong inhibitor of angiogenesis
dc.creator.none.fl_str_mv Rodríguez, Patricia
Higueras López, M. Ángeles
Fierro-Fernández, Marta
Monsalve, María
Rodríguez-Pascual, Fernando
Lamas Peláez, Santiago
author Rodríguez, Patricia
author_facet Rodríguez, Patricia
Higueras López, M. Ángeles
Fierro-Fernández, Marta
Monsalve, María
Rodríguez-Pascual, Fernando
Lamas Peláez, Santiago
author_role author
author2 Higueras López, M. Ángeles
Fierro-Fernández, Marta
Monsalve, María
Rodríguez-Pascual, Fernando
Lamas Peláez, Santiago
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Comunidad de Madrid
Ministerio de Ciencia e Innovación (España)
dc.subject.none.fl_str_mv Angiogenesis
Delta-like 1
Pref-1
Endothelium
NOTCH
topic Angiogenesis
Delta-like 1
Pref-1
Endothelium
NOTCH
description El pdf es el manuscrito de autor.-- et al.
publishDate 2011
dc.date.none.fl_str_mv 2011
2013
2013
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/75145
url http://hdl.handle.net/10261/75145
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
S2006/BIO-0194/CARDIOVREP
http://dx.doi.org/10.1093/cvr/cvr296
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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