EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity.

Endothelial integrity is vital for homeostasis and adjusted to tissue demands. Although fluid uptake by lymphatic capillaries is a critical attribute of the lymphatic vasculature, the barrier function of collecting lymphatic vessels is also important by ensuring efficient fluid drainage as well as l...

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Autores: Frye, Maike, Stritt, Simon, Ortsäter, Henrik, Hernandez Vasquez, Magda, Kaakinen, Mika, Vicente, Andres, Wiseman, John, Eklund, Lauri, Vestweber, Dietmar, Mäkinen, Taija, Martinez Torrecuadrada, Jorge Luis
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/12406
Acceso en línea:http://hdl.handle.net/20.500.12105/12406
Access Level:acceso abierto
Palabra clave:Homeostasis
Signal Transduction
Animals
Claudin-5
Endothelial Cells
Ephrin-B2
Gene Deletion
Intercellular Junctions
Lymphatic Vessels
Mice
Receptor, EphB4
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/12406
network_acronym_str ES
network_name_str España
repository_id_str
spelling EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity.Frye, MaikeStritt, SimonOrtsäter, HenrikHernandez Vasquez, MagdaKaakinen, MikaVicente, AndresWiseman, JohnEklund, LauriVestweber, DietmarMäkinen, TaijaMartinez Torrecuadrada, Jorge LuisHomeostasisSignal TransductionAnimalsClaudin-5Endothelial CellsEphrin-B2Gene DeletionIntercellular JunctionsLymphatic VesselsMiceReceptor, EphB4Endothelial integrity is vital for homeostasis and adjusted to tissue demands. Although fluid uptake by lymphatic capillaries is a critical attribute of the lymphatic vasculature, the barrier function of collecting lymphatic vessels is also important by ensuring efficient fluid drainage as well as lymph node delivery of antigens and immune cells. Here, we identified the transmembrane ligand EphrinB2 and its receptor EphB4 as critical homeostatic regulators of collecting lymphatic vessel integrity. Conditional gene deletion in mice revealed that EphrinB2/EphB4 signalling is dispensable for blood endothelial barrier function, but required for stabilization of lymphatic endothelial cell (LEC) junctions in different organs of juvenile and adult mice. Studies in primary human LECs further showed that basal EphrinB2/EphB4 signalling controls junctional localisation of the tight junction protein CLDN5 and junction stability via Rac1/Rho-mediated regulation of cytoskeletal contractility. EphrinB2/EphB4 signalling therefore provides a potential therapeutic target to selectively modulate lymphatic vessel permeability and function.eLife Sciences PublicationsSwedish Cancer Society (Cancerfonden)Knut and Alice Wallenberg FoundationSwedish Research CouncilUnión Europea. Comisión Europea. H2020Deutsche Forschungsgemeinschaft (Alemania)European Molecular Biology OrganizationComunidad de Madrid (España)20212021-03-2320202020-09-0820202020-09-08journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/12406reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengNot available ES BIPEDD2 S2011open accesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial-CompartirIgual 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/124062026-06-12T12:43:37Z
dc.title.none.fl_str_mv EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity.
title EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity.
spellingShingle EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity.
Frye, Maike
Homeostasis
Signal Transduction
Animals
Claudin-5
Endothelial Cells
Ephrin-B2
Gene Deletion
Intercellular Junctions
Lymphatic Vessels
Mice
Receptor, EphB4
title_short EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity.
title_full EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity.
title_fullStr EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity.
title_full_unstemmed EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity.
title_sort EphrinB2-EphB4 signalling provides Rho-mediated homeostatic control of lymphatic endothelial cell junction integrity.
dc.creator.none.fl_str_mv Frye, Maike
Stritt, Simon
Ortsäter, Henrik
Hernandez Vasquez, Magda
Kaakinen, Mika
Vicente, Andres
Wiseman, John
Eklund, Lauri
Vestweber, Dietmar
Mäkinen, Taija
Martinez Torrecuadrada, Jorge Luis
author Frye, Maike
author_facet Frye, Maike
Stritt, Simon
Ortsäter, Henrik
Hernandez Vasquez, Magda
Kaakinen, Mika
Vicente, Andres
Wiseman, John
Eklund, Lauri
Vestweber, Dietmar
Mäkinen, Taija
Martinez Torrecuadrada, Jorge Luis
author_role author
author2 Stritt, Simon
Ortsäter, Henrik
Hernandez Vasquez, Magda
Kaakinen, Mika
Vicente, Andres
Wiseman, John
Eklund, Lauri
Vestweber, Dietmar
Mäkinen, Taija
Martinez Torrecuadrada, Jorge Luis
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Swedish Cancer Society (Cancerfonden)
Knut and Alice Wallenberg Foundation
Swedish Research Council
Unión Europea. Comisión Europea. H2020
Deutsche Forschungsgemeinschaft (Alemania)
European Molecular Biology Organization
Comunidad de Madrid (España)
dc.subject.none.fl_str_mv Homeostasis
Signal Transduction
Animals
Claudin-5
Endothelial Cells
Ephrin-B2
Gene Deletion
Intercellular Junctions
Lymphatic Vessels
Mice
Receptor, EphB4
topic Homeostasis
Signal Transduction
Animals
Claudin-5
Endothelial Cells
Ephrin-B2
Gene Deletion
Intercellular Junctions
Lymphatic Vessels
Mice
Receptor, EphB4
description Endothelial integrity is vital for homeostasis and adjusted to tissue demands. Although fluid uptake by lymphatic capillaries is a critical attribute of the lymphatic vasculature, the barrier function of collecting lymphatic vessels is also important by ensuring efficient fluid drainage as well as lymph node delivery of antigens and immune cells. Here, we identified the transmembrane ligand EphrinB2 and its receptor EphB4 as critical homeostatic regulators of collecting lymphatic vessel integrity. Conditional gene deletion in mice revealed that EphrinB2/EphB4 signalling is dispensable for blood endothelial barrier function, but required for stabilization of lymphatic endothelial cell (LEC) junctions in different organs of juvenile and adult mice. Studies in primary human LECs further showed that basal EphrinB2/EphB4 signalling controls junctional localisation of the tight junction protein CLDN5 and junction stability via Rac1/Rho-mediated regulation of cytoskeletal contractility. EphrinB2/EphB4 signalling therefore provides a potential therapeutic target to selectively modulate lymphatic vessel permeability and function.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-09-08
2020
2020-09-08
2021
2021-03-23
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/12406
url http://hdl.handle.net/20.500.12105/12406
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Not available ES BIPEDD2 S2011
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-CompartirIgual 4.0 Internacional
http://creativecommons.org/licenses/by-nc-sa/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-CompartirIgual 4.0 Internacional
http://creativecommons.org/licenses/by-nc-sa/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv eLife Sciences Publications
publisher.none.fl_str_mv eLife Sciences Publications
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869418530067185664
score 15.81155

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