Aristorena, MikelGallardo-Vara, EunateVicen, Matejde Las Casas-Engel, MateoOjeda-Fernandez, LuisaNieto, ConcepcionBlanco, Francisco JValbuena-Diez, Ana CBotella, Luisa MNachtigal, PetrCorbi, Angel LColmenares, MariaBernabeu, Carmelo2023-01-252023-01-252019-06-18Aristorena 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.http://hdl.handle.net/10668/14181Upon 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/MMP-12endoglinendothelial cellsinflammationmacrophagesmonocytesAnimalsCells, CulturedDisease Models, AnimalDisease SusceptibilityEndoglinEndothelial CellsGene ExpressionGranulocyte-Macrophage Colony-Stimulating FactorHumansInflammationInflammation MediatorsMacrophage Colony-Stimulating FactorMacrophagesMatrix Metalloproteinase 12MiceModels, Biologicalresearch article31242676open accessCélulas cultivadasCélulas endotelialesEndoglinaFactor estimulante de colonias de granulocitos y macrófagosFactor estimulante de colonias de macrófagosMacrófagosMediadores de inflamaciónMetaloproteinasa 12 de la matrizModelos animales de enfermedadModelos biológicosSusceptibilidad a enfermedades10.3390/ijms201231071422-0067PMC6627183https://www.mdpi.com/1422-0067/20/12/3107/pdf?version=1561465408https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627183/pdf