Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/139717
Title: ROLE OF JAG1-EXTRACELLULAR VESICLES ON ANGIOGENESIS
Authors: TAN EVAN
Keywords: Angiogenesis, Notch signalling, Extracellular vesicles
Issue Date: 21-Aug-2017
Source: TAN EVAN (2017-08-21). ROLE OF JAG1-EXTRACELLULAR VESICLES ON ANGIOGENESIS. ScholarBank@NUS Repository.
Abstract: Notch signalling is an evolutionary conserved pathway that is essential in development. Jagged1(JAG1) and Delta-like ligand 4 (DLL4) are Notch ligands that regulate angiogenesis by controlling endothelial cell differentiation, vascular development and maturation. It was previously shown that DLL4 could bypass its canonical contact-dependent signalling to influence Notch signalling at a distance when packaged into extracellular vesicles (EVs). This led to the hypothesis that JAG1 could be packaged into EVs, whereby it could influence angiogenesis in a paracrine fashion. In this work, I have demonstrated that JAG1 can be packaged into EVs. Next, to study the effect of JAG1-EVs on angiogenesis, I isolated JAG1-EVs from JAG1 overexpressing HEK293T cells. I found that JAG1-EVs inhibited Notch signalling in endothelial cells (ECs), leading to the inhibition of EC proliferation, migration and sprouting. I showed that JAG1-EVs inhibited Notch signalling by promoting the degradation of NOTCH1-intracellular domain (ICD) in a process mediated by JAG1-ICD. These findings reveal a novel role of EV-mediated JAG1 function in angiogenesis.
URI: http://scholarbank.nus.edu.sg/handle/10635/139717
Appears in Collections:Ph.D Theses (Open)

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