title: Differential apicobasal VEGF signaling at vascular blood-neural barriers.
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.
authors.affiliation: Department of Cell Biology, UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Natalie
authors.initials: N
authors.lastname: Hudson
authors.affiliation: Department of Cell Biology, UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Powner
authors.affiliation: 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.
authors.forename: Mosharraf H
authors.initials: MH
authors.lastname: Sarker
authors.affiliation: Department of Cell Biology, UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Burgoyne
authors.affiliation: Neurovascular Genetics Laboratory, Smurfit Institute of Genetics, Lincoln Place Gate, Trinity College, Dublin 2, Ireland.
authors.forename: Matthew
authors.initials: M
authors.lastname: Campbell
authors.affiliation: Department of Cell Biology, UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Zoe K
authors.initials: ZK
authors.lastname: Ockrim
authors.affiliation: Department of Cell Biology, UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Roberta
authors.initials: R
authors.lastname: Martinelli
authors.affiliation: Department of Cell Biology, UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: Clare E
authors.initials: CE
authors.lastname: Futter
authors.affiliation: Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, 1160 West Michigan Street, Indianapolis, IN 46202, USA.
authors.forename: Maria B
authors.initials: MB
authors.lastname: Grant
authors.affiliation: Cardiovascular Division, King's College London, 150 Stamford Street, London SE1 9NH, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Fraser
authors.affiliation: Department of Ocular Biology and Therapeutics, UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: David T
authors.initials: DT
authors.lastname: Shima
authors.affiliation: Department of Cell Biology, UCL Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.
authors.forename: John
authors.initials: J
authors.lastname: Greenwood
authors.affiliation: 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.
authors.forename: Patric
authors.initials: P
authors.lastname: Turowski
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation; D009474:Neurons / Q000378:metabolism*; D010539:Permeability; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D048051:p38 Mitogen-Activated Protein Kinases