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Dev Cell. 2014 Sep 8;30(5):541-52. doi: 10.1016/j.devcel.2014.06.027. Epub 2014 Aug 28.

Differential apicobasal VEGF signaling at vascular blood-neural barriers.

Author information

1
Department of Cell Biology, UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
2
Department of Cell Biology, UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK; Cardiovascular Division, King's College London, 150 Stamford Street, London SE1 9NH, UK.
3
Neurovascular Genetics Laboratory, Smurfit Institute of Genetics, Lincoln Place Gate, Trinity College, Dublin 2, Ireland.
4
Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, 1160 West Michigan Street, Indianapolis, IN 46202, USA.
5
Cardiovascular Division, King's College London, 150 Stamford Street, London SE1 9NH, UK.
6
Department of Ocular Biology and Therapeutics, UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
7
Department of Cell Biology, UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK. Electronic address: p.turowski@ucl.ac.uk.

Abstract

The vascular endothelium operates in a highly polarized environment, but to date there has been little exploration of apicobasal polarization of its signaling. We show that VEGF-A, histamine, IGFBP3, and LPA trigger unequal endothelial responses when acting from the circulation or the parenchymal side at blood-neural barriers. For VEGF-A, highly polarized receptor distribution contributed to distinct signaling patterns: VEGFR2, which was found to be predominantly abluminal, mediated increased permeability via p38; in contrast, luminal VEGFR1 led to Akt activation and facilitated cytoprotection. Importantly, such differential apicobasal signaling and VEGFR distribution were found in the microvasculature of brain and retina but not lung, indicating that endothelial cells at blood-neural barriers possess specialized signaling compartments that assign different functions depending on whether an agonist is tissue or blood borne.

PMID:
25175707
PMCID:
PMC4160345
DOI:
10.1016/j.devcel.2014.06.027
[Indexed for MEDLINE]
Free PMC Article
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