Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10752018 | Biochemical and Biophysical Research Communications | 2015 | 7 Pages |
Abstract
During angiogenesis, endothelial cells (ECs1) initiate new blood vessel growth and invade into the extracellular matrix (ECM). Membrane type-1 matrix metalloproteinase (MT1-MMP) facilitates this process and translocates to the plasma membrane following activation to promote ECM cleavage. The N-terminal pro-domain within MT1-MMP must be processed for complete activity of the proteinase. This study investigated whether MT1-MMP activation was altered by sphingosine 1-phosphate (S1P) and wall shear stress (WSS), which combine to stimulate EC invasion in three dimensional (3D) collagen matrices. MT1-MMP was activated rapidly and completely by WSS but not S1P. Proprotein convertases (PCs) promoted MT1-MMP processing, prompting us to test whether WSS or S1P treatments increased PC activity. Like MT1-MMP, PC activity increased with WSS, while S1P had no effect. A pharmacological PC inhibitor completely blocked S1P- and WSS-induced EC invasion and MT1-MMP translocation to the plasma membrane. Further, a recombinant PC inhibitor reduced MT1-MMP activation and decreased lumen formation in invading ECs, a process known to be controlled by MT1-MMP. Thus, we conclude that PC and MT1-MMP activation are mechanosensitive events that are required for EC invasion into 3D collagen matrices.
Keywords
ECMWSSMT1-MMPS1PThree-dimensionalGFPHUVECGAPDHFGFECsAngiogenesisWall shear stresssphingosine 1-phosphateSproutingHuman umbilical vein endothelial cellEndothelial cellsVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)fibroblast growth factorFurinExtracellular matrixmembrane type-1 matrix metalloproteinaseMechanotransductiongreen fluorescent proteinproprotein convertaseGlyceraldehyde phosphate dehydrogenase
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Authors
Hojin Kang, Camille L. Duran, Colette A. Abbey, Roland R. Kaunas, Kayla J. Bayless,