MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells
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. View Full-Text
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Aristorena, M.; Gallardo-Vara, E.; Vicen, M.; de Las Casas-Engel, M.; Ojeda-Fernandez, L.; Nieto, C.; Blanco, F.J.; Valbuena-Diez, A.C.; Botella, L.M.; Nachtigal, P.; Corbi, A.L.; Colmenares, M.; Bernabeu, C. MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells. Int. J. Mol. Sci. 2019, 20, 3107.
Aristorena M, Gallardo-Vara E, Vicen M, de Las Casas-Engel M, Ojeda-Fernandez L, Nieto C, Blanco FJ, Valbuena-Diez AC, Botella LM, Nachtigal P, Corbi AL, Colmenares M, Bernabeu C. MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells. International Journal of Molecular Sciences. 2019; 20(12):3107.Chicago/Turabian Style
Aristorena, Mikel; Gallardo-Vara, Eunate; Vicen, Matej; de Las Casas-Engel, Mateo; Ojeda-Fernandez, Luisa; Nieto, Concepción; Blanco, Francisco J.; Valbuena-Diez, Ana C.; Botella, Luisa M.; Nachtigal, Petr; Corbi, Angel L.; Colmenares, María; Bernabeu, Carmelo. 2019. "MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells." Int. J. Mol. Sci. 20, no. 12: 3107.
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