RT Journal Article
T1 MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells.
A1 Aristorena, Mikel
A1 Gallardo-Vara, Eunate
A1 Vicen, Matej
A1 de Las Casas-Engel, Mateo
A1 Ojeda-Fernandez, Luisa
A1 Nieto, Concepcion
A1 Blanco, Francisco J
A1 Valbuena-Diez, Ana C
A1 Botella, Luisa M
A1 Nachtigal, Petr
A1 Corbi, Angel L
A1 Colmenares, Maria
A1 Bernabeu, Carmelo
K1 MMP-12
K1 endoglin
K1 endothelial cells
K1 inflammation
K1 macrophages
K1 monocytes
AB 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.
PB MDPI AG
YR 2019
FD 2019-06-18
LK http://hdl.handle.net/10668/14181
UL http://hdl.handle.net/10668/14181
LA en
NO Aristorena M, Gallardo-Vara E, Vicen M, de Las Casas-Engel M, Ojeda-Fernandez L, Nieto C, et al. MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells. Int J Mol Sci. 2019 Jun 25;20(12):3107.
NO 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.
DS RISalud
RD Apr 8, 2025