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Title

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

AuthorsAristorena, Mikel; Gallardo-Vara, Eunate CSIC ORCID; Vicen, Matej; Casas-Engel, Mateo de las CSIC; Ojeda-Fernández, María Luisa; Nieto, Concha CSIC ORCID ; Blanco, Francisco J. CSIC ORCID ; Valbuena-Díez, Ana C. CSIC; Botella, Luisa María CSIC ORCID ; Nachtigal, Petr; Corbí, Angel L. CSIC ORCID ; Colmenares, María CSIC ORCID ; Bernabéu, Carmelo CSIC ORCID
KeywordsMonocytes
Macrophages
Endothelial cells
Inflammation
MMP-12
Endoglin
Issue Date25-Jun-2019
PublisherMultidisciplinary Digital Publishing Institute
CitationInternational Journal of Molecular Sciences 20 (12): 3107 (2019)
AbstractUpon 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.
Publisher version (URL)https://doi.org/10.3390/ijms20123107
URIhttp://hdl.handle.net/10261/185057
DOIhttp://dx.doi.org/10.3390/ijms20123107
E-ISSN1422-0067
Appears in Collections:(CIB) Artículos
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