Journal
INTEGRATIVE BIOLOGY
Volume 10, Issue 11, Pages 719-726Publisher
OXFORD UNIV PRESS
DOI: 10.1039/c8ib00036k
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Funding
- 1Valve consortium - Netherlands Cardiovascular Research Initiative [CVON 2012-01]
- Dutch Heart Foundation
- Dutch Federation of University Medical Centers
- Netherlands Organization for Health Research and Development
- Royal Netherlands Academy of Sciences
- ForceMorph project - ERC [771168]
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Notch signaling and blood flow regulate vascular formation and maturation, but how shear stress affects the different components of the Notch pathway in endothelial cells is poorly understood. We show that laminar shear stress results in a ligand specific gene expression profile in endothelial cells (HUVEC). JAG1 expression increases while DLL4 expression decreases. Jagged1 shows a unique response by clustering intracellularly six to nine hours after the onset of flow. The formation of the Jagged1 clusters requires protein production, ER export and endocytosis. Clustering is associated with reduced membrane levels but is not affected by Notch signaling activity. Jagged1 relocalization is reversible, the clusters disappear and membrane levels increase upon removal of shear stress. We further demonstrate that the signaling potential of endothelial cells is enhanced after exposure to shear stress. Together we demonstrate a Jagged1 specific shear stress response for Notch signaling in endothelial cells.
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