MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells
Abstract
:1. Introduction
2. Results
2.1. Inhibitory Effect of the GM-MΦ Secretome on Endothelial Tubulogenesis
2.2. Expression of Endoglin in Monocyte-Derived MΦ
2.3. Endoglin Shedding from GM-MΦ Cell Surface is Mediated by MMP-12
2.4. MMP-12 Induces Soluble Endoglin Release in Endothelial Cells
2.5. MMP-12 Induces Soluble Endoglin Release in an in Vivo Mouse Model of Inflammation
3. Discussion
4. Materials and Methods
4.1. Macrophage Culture and Differentiation
4.2. Endothelial Cell Culture
4.3. Tube Formation and wound Healing Assays
4.4. Quantitative RT-PCR
4.5. Immunodetection Assays
4.6. Recombinant MMP-12 Activity
4.7. Generation of the MMP-12 Expression Vector
4.8. Transient Transfection Assays
4.9. Casein Zymography
4.10. In Vivo Inflammatory Response and Inhibition of MMP-12 in a Mouse Model
4.11. Statistical Analysis
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
FBS | Fetal Bovine Serum |
GM-CSF | Granulocyte-Macrophage Colony-Stimulating Factor |
GM-MΦ | GM-CSF monocyte-derived macrophage |
HHT | Hereditary Hemorrhagic Telangiectasia |
HUVECs | Human Umbilical Vein Endothelial Cells |
MΦ | Macrophages |
M-CSF | Macrophage Colony Stimulating Factor 1 |
M-MΦ | M-CSF monocyte-derived macrophage |
MMP | Matrix Metalloproteinase |
PBMCs | Peripheral Blood Mononuclear Cells |
sEng | soluble Endoglin |
SDS | Sodium dodecyl sulfate |
qRT-PCR | quantitative Real-Time PCR |
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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.; et al. MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells. Int. J. Mol. Sci. 2019, 20, 3107. https://doi.org/10.3390/ijms20123107
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, et al. MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells. International Journal of Molecular Sciences. 2019; 20(12):3107. https://doi.org/10.3390/ijms20123107
Chicago/Turabian StyleAristorena, Mikel, Eunate Gallardo-Vara, Matej Vicen, Mateo de Las Casas-Engel, Luisa Ojeda-Fernandez, Concepción Nieto, Francisco J. Blanco, Ana C. Valbuena-Diez, Luisa M. Botella, Petr Nachtigal, and et al. 2019. "MMP-12, Secreted by Pro-Inflammatory Macrophages, Targets Endoglin in Human Macrophages and Endothelial Cells" International Journal of Molecular Sciences 20, no. 12: 3107. https://doi.org/10.3390/ijms20123107