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MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells
dc.contributor.author | Aristorena, Mikel | |
dc.contributor.author | Gallardo-Vara, Eunate | |
dc.contributor.author | Vicen, Matej | |
dc.contributor.author | de Las Casas-Engel, Mateo | |
dc.contributor.author | Ojeda-Fernandez, Luisa | |
dc.contributor.author | Nieto, Concepción | |
dc.contributor.author | Blanco, Francisco J. | |
dc.contributor.author | Valbuena-Diez, Ana C. | |
dc.contributor.author | Botella, Luisa M. | |
dc.contributor.author | Nachtigal, Petr | |
dc.contributor.author | Corbi, Angel L. | |
dc.contributor.author | Colmenares, María | |
dc.contributor.author | Bernabeu, Carmelo | |
dc.date.accessioned | 2019-10-11T11:14:06Z | |
dc.date.available | 2019-10-11T11:14:06Z | |
dc.date.issued | 2019-06-02 | |
dc.identifier.citation | Aristorena, M., Gallardo-Vara, E., Vicen, M., de Las Casas-Engel, M., Ojeda-Fernandez, L., Nieto, C., ... & Corbi, A. L. (2019). MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells. International journal of molecular sciences, 20(12), 3107. | es_ES |
dc.identifier.uri | http://hdl.handle.net/10481/57311 | |
dc.description.abstract | Upon inflammation, monocyte-derived macrophages (MF) 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 e cient initial response (GM-MF) and a good resolution (M-MF) of the inflammatory process. The functional activity of polarized MF 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 MF 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 MF secretome involved in the shedding of soluble endoglin. We find that the GM-MF secretome contains metalloprotease 12 (MMP-12), a GM-MF specific marker that may account for the anti-angiogenic activity of the GM-MF secretome. Cell surface endoglin is present in both GM-MF and M-MF, but soluble endoglin is only detected in GM-MF 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 MF and endothelial cells. These data demonstrate a direct correlation between GM-MF polarization, MMP-12, and soluble endoglin expression and function. By targeting endothelial cells, MMP-12 may represent a novel mediator involved in vascular homeostasis. | es_ES |
dc.description.sponsorship | Ministerio de Ciencia, Innovación y Universidades of Spain (SAF2013-43421-R to C.B.; SAF2017-83785-R and SAF2014-23801 to A.L.C.) | es_ES |
dc.description.sponsorship | Consejo Superior de Investigaciones Cientificas (201920E022 to C.B.) | es_ES |
dc.description.sponsorship | Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER; ISCIII-CB06/07/0038 to C.B.) | es_ES |
dc.description.sponsorship | Czech Republic Specific University Research (SVV-260414 to P.N.) | es_ES |
dc.description.sponsorship | CIBERER is an initiative of the Instituto de Salud Carlos III (ISCIII) of Spain supported by FEDER funds | es_ES |
dc.description.sponsorship | M.A. was funded with a fellowship from Ministerio de Ciencia e Innovación (BES-2008-003888) | es_ES |
dc.description.sponsorship | M.V. was supported by a short-term mobility fellowship from the European Erasmus Programme | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | MDPI | es_ES |
dc.rights | Atribución 3.0 España | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | Monocytes | es_ES |
dc.subject | Macrophages | es_ES |
dc.subject | Endothelial cells | es_ES |
dc.subject | Inflammation | es_ES |
dc.subject | MMP-12 | es_ES |
dc.subject | endoglin | es_ES |
dc.title | MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es_ES |
dc.identifier.doi | 10.3390/ijms20123107 |