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Polarised VEGFA Signalling at Vascular Blood–Neural Barriers

Dragoni, S; Turowski, P; (2018) Polarised VEGFA Signalling at Vascular Blood–Neural Barriers. International Journal of Molecular Sciences , 19 (5) , Article 1378. 10.3390/ijms19051378. Green open access

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Abstract

At blood–neural barriers, endothelial VEGFA signalling is highly polarised, with entirely different responses being triggered by luminal or abluminal stimulation. These recent findings were made in a field which is still in its mechanistic infancy. For a long time, endothelial polarity has intuitively been presumed, and likened to that of epithelial cells, but rarely demonstrated. In the cerebral and the retinal microvasculature, the uneven distribution of VEGF receptors 1 and 2, with the former predominant on the luminal and the latter on the abluminal face of the endothelium, leads to a completely polarised signalling response to VEGFA. Luminal VEGFA activates VEGFR1 homodimers and AKT, leading to a cytoprotective response, whilst abluminal VEGFA induces vascular leakage via VEGFR2 homodimers and p38. Whilst these findings do not provide a complete picture of VEGFA signalling in the microvasculature—there are still unclear roles for heterodimeric receptor complexes as well as co-receptors—they provide essential insight into the adaptation of vascular systems to environmental cues that are naturally different, depending on whether they are present on the blood or tissue side. Importantly, sided responses are not only restricted to VEGFA, but exist for other important vasoactive agents.

Type: Article
Title: Polarised VEGFA Signalling at Vascular Blood–Neural Barriers
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/ijms19051378
Publisher version: https://doi.org/10.3390/ijms19051378
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: VEGF, endothelial cells, polarity
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10049302
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