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01-08-2018 | Original Paper

Extracellular vesicle-carried Jagged-1 inhibits HUVEC sprouting in a 3D microenvironment

Authors: Evan Tan, Harry H. Asada, Ruowen Ge

Published in: Angiogenesis | Issue 3/2018

Abstract

NOTCH signalling is an evolutionarily conserved juxtacrine signalling pathway that is essential in development. Jagged1 (JAG1) and Delta-like ligand 4 (DLL4) are transmembrane NOTCH ligands that regulate angiogenesis by controlling endothelial cell (EC) differentiation, vascular development and maturation. In addition, DLL4 could bypass its canonical cell–cell contact-dependent signalling to influence NOTCH signalling and angiogenesis at a distance when it is packaged into extracellular vesicles (EVs). However, it is not clear whether JAG1 could also be packaged into EVs to influence NOTCH signalling and angiogenesis. In this work, we demonstrate that JAG1 is also packaged into EVs. We present evidence that JAG1-EVs inhibit NOTCH signalling and regulate EC behaviour and function. JAG1-EVs inhibited VEGF-induced HUVEC proliferation and migration in 2D culture condition and suppressed sprouting in a 3D microfluidic microenvironment. JAG1-EV treatment of HUVECs leads to a reduction of Notch1 intracellular domain (N1-ICD), and the proteasome and the intracellular domain of JAG1 (JAG1-ICD) are both required for this reduction to occur. These findings reveal a novel mechanism of JAG1 function in NOTCH signalling and ECs through EVs.

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Title: Extracellular vesicle-carried Jagged-1 inhibits HUVEC sprouting in a 3D microenvironment
Authors: Evan Tan
Harry H. Asada
Ruowen Ge
Publication date: 01-08-2018
Publisher: Springer Netherlands
Published in: Angiogenesis / Issue 3/2018
Print ISSN: 0969-6970
Electronic ISSN: 1573-7209
DOI: https://doi.org/10.1007/s10456-018-9609-6

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