MMP-12, secreted by pro-ìnflammatory macrophages, targets endoglin in human macrophages and endothelial cells

Upon inflammation, monocyte-derived macrophages (MΦ) infiltrate blood vessels to regulate several processes involved in vascular pathophysiology. However, little is known about the mediators involved. Macrophage polarization is crucial for a fast and efficient initial response (GM-MΦ) and a good res...

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Autores: Aristorena, Mikel, Gallardo-Vara, Eunate, Vicen, Matej, Casas-Engel, Mateo de las, Ojeda-Fernández, María Luisa, Nieto, Concha, Blanco, Francisco J., Valbuena-Díez, Ana C., Botella, Luisa María, Nachtigal, Petr, Corbí, Angel L., Colmenares, María, Bernabéu, Carmelo
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/185057
Acesso em linha:http://hdl.handle.net/10261/185057
Access Level:acceso abierto
Palavra-chave:Monocytes
Macrophages
Endothelial cells
Inflammation
MMP-12
Endoglin
id ES_7afa90bbd11bb31155a3a33fe30ade52
oai_identifier_str oai:digital.csic.es:10261/185057
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv MMP-12, secreted by pro-ìnflammatory macrophages, targets endoglin in human macrophages and endothelial cells
title MMP-12, secreted by pro-ìnflammatory macrophages, targets endoglin in human macrophages and endothelial cells
spellingShingle MMP-12, secreted by pro-ìnflammatory macrophages, targets endoglin in human macrophages and endothelial cells
Aristorena, Mikel
Monocytes
Macrophages
Endothelial cells
Inflammation
MMP-12
Endoglin
title_short MMP-12, secreted by pro-ìnflammatory macrophages, targets endoglin in human macrophages and endothelial cells
title_full MMP-12, secreted by pro-ìnflammatory macrophages, targets endoglin in human macrophages and endothelial cells
title_fullStr MMP-12, secreted by pro-ìnflammatory macrophages, targets endoglin in human macrophages and endothelial cells
title_full_unstemmed MMP-12, secreted by pro-ìnflammatory macrophages, targets endoglin in human macrophages and endothelial cells
title_sort MMP-12, secreted by pro-ìnflammatory macrophages, targets endoglin in human macrophages and endothelial cells
dc.creator.none.fl_str_mv Aristorena, Mikel
Gallardo-Vara, Eunate
Vicen, Matej
Casas-Engel, Mateo de las
Ojeda-Fernández, María Luisa
Nieto, Concha
Blanco, Francisco J.
Valbuena-Díez, Ana C.
Botella, Luisa María
Nachtigal, Petr
Corbí, Angel L.
Colmenares, María
Bernabéu, Carmelo
author Aristorena, Mikel
author_facet Aristorena, Mikel
Gallardo-Vara, Eunate
Vicen, Matej
Casas-Engel, Mateo de las
Ojeda-Fernández, María Luisa
Nieto, Concha
Blanco, Francisco J.
Valbuena-Díez, Ana C.
Botella, Luisa María
Nachtigal, Petr
Corbí, Angel L.
Colmenares, María
Bernabéu, Carmelo
author_role author
author2 Gallardo-Vara, Eunate
Vicen, Matej
Casas-Engel, Mateo de las
Ojeda-Fernández, María Luisa
Nieto, Concha
Blanco, Francisco J.
Valbuena-Díez, Ana C.
Botella, Luisa María
Nachtigal, Petr
Corbí, Angel L.
Colmenares, María
Bernabéu, Carmelo
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Agencia Estatal de Investigación (España)
Ministerio de Economía y Competitividad (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Instituto de Salud Carlos III
European Commission
Ministerio de Ciencia e Innovación (España)
Consejo Superior de Investigaciones Científicas (España)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Monocytes
Macrophages
Endothelial cells
Inflammation
MMP-12
Endoglin
topic Monocytes
Macrophages
Endothelial cells
Inflammation
MMP-12
Endoglin
description Upon inflammation, monocyte-derived macrophages (MΦ) infiltrate blood vessels to regulate several processes involved in vascular pathophysiology. However, little is known about the mediators involved. Macrophage polarization is crucial for a fast and efficient initial response (GM-MΦ) and a good resolution (M-MΦ) of the inflammatory process. The functional activity of polarized MΦ is exerted mainly through their secretome, which can target other cell types, including endothelial cells. Endoglin (CD105) is a cell surface receptor expressed by endothelial cells and MΦ that is markedly upregulated in inflammation and critically involved in angiogenesis. In addition, a soluble form of endoglin with anti-angiogenic activity has been described in inflammation-associated pathologies. The aim of this work was to identify components of the MΦ secretome involved in the shedding of soluble endoglin. We find that the GM-MΦ secretome contains metalloprotease 12 (MMP-12), a GM-MΦ specific marker that may account for the anti-angiogenic activity of the GM-MΦ secretome. Cell surface endoglin is present in both GM-MΦ and M-MΦ, but soluble endoglin is only detected in GM-MΦ culture supernatants. Moreover, MMP-12 is responsible for the shedding of soluble endoglin in vitro and in vivo by targeting membrane-bound endoglin in both MΦ and endothelial cells. These data demonstrate a direct correlation between GM-MΦ polarization, MMP-12, and soluble endoglin expression and function. By targeting endothelial cells, MMP-12 may represent a novel mediator involved in vascular homeostasis.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019
2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/185057
url http://hdl.handle.net/10261/185057
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
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SAF2017-83785-R/AEI/10.13039/501100011033
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-43421-R
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/SAF2017-83785-R
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-23801
https://doi.org/10.3390/ijms20123107
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
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
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spelling MMP-12, secreted by pro-ìnflammatory macrophages, targets endoglin in human macrophages and endothelial cellsAristorena, MikelGallardo-Vara, EunateVicen, MatejCasas-Engel, Mateo de lasOjeda-Fernández, María LuisaNieto, ConchaBlanco, Francisco J.Valbuena-Díez, Ana C.Botella, Luisa MaríaNachtigal, PetrCorbí, Angel L.Colmenares, MaríaBernabéu, CarmeloMonocytesMacrophagesEndothelial cellsInflammationMMP-12EndoglinUpon inflammation, monocyte-derived macrophages (MΦ) infiltrate blood vessels to regulate several processes involved in vascular pathophysiology. However, little is known about the mediators involved. Macrophage polarization is crucial for a fast and efficient initial response (GM-MΦ) and a good resolution (M-MΦ) of the inflammatory process. The functional activity of polarized MΦ is exerted mainly through their secretome, which can target other cell types, including endothelial cells. Endoglin (CD105) is a cell surface receptor expressed by endothelial cells and MΦ that is markedly upregulated in inflammation and critically involved in angiogenesis. In addition, a soluble form of endoglin with anti-angiogenic activity has been described in inflammation-associated pathologies. The aim of this work was to identify components of the MΦ secretome involved in the shedding of soluble endoglin. We find that the GM-MΦ secretome contains metalloprotease 12 (MMP-12), a GM-MΦ specific marker that may account for the anti-angiogenic activity of the GM-MΦ secretome. Cell surface endoglin is present in both GM-MΦ and M-MΦ, but soluble endoglin is only detected in GM-MΦ culture supernatants. Moreover, MMP-12 is responsible for the shedding of soluble endoglin in vitro and in vivo by targeting membrane-bound endoglin in both MΦ and endothelial cells. These data demonstrate a direct correlation between GM-MΦ polarization, MMP-12, and soluble endoglin expression and function. By targeting endothelial cells, MMP-12 may represent a novel mediator involved in vascular homeostasis.This research was funded by grants from Ministerio de Ciencia, Innovación y Universidades of Spain (SAF2013-43421-R to C.B.; SAF2017-83785-R and SAF2014-23801 to A.L.C.), Consejo Superior de Investigaciones Cientificas (201920E022 to C.B.), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER; ISCIII-CB06/07/0038 to C.B.), and Czech Republic Specific University Research (SVV-260414 to P.N.). CIBERER is an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain supported by FEDER funds. M.A. was funded with a fellowship from Ministerio de Ciencia e Innovación (BES-2008-003888). M.V. was supported by a short-term mobility fellowship from the European Erasmus Programme.Peer reviewedMultidisciplinary Digital Publishing InstituteAgencia Estatal de Investigación (España)Ministerio de Economía y Competitividad (España)Ministerio de Ciencia, Innovación y Universidades (España)Instituto de Salud Carlos IIIEuropean CommissionMinisterio de Ciencia e Innovación (España)Consejo Superior de Investigaciones Científicas (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2019201920192019info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/185057reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#SAF2017-83785-R/AEI/10.13039/501100011033info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2013-43421-Rinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/SAF2017-83785-Rinfo:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2014-23801https://doi.org/10.3390/ijms20123107Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1850572026-05-22T06:33:51Z
score 15,811543

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