Differential apicobasal VEGF signaling at vascular blood-neural barriers

Natalie Hudson, Michael B. Powner, Mosharraf H. Sarker, Thomas Burgoyne, Matthew Campbell, Zoe K. Ockrim, Roberta Martinelli, Clare E. Futter, Maria B. Grant, Paul A. Fraser, David T. Shima, John Greenwood, Patric Turowski

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The vascular endothelium operates in a highly polarized environment, but to date there has been littleexploration 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.

Original languageEnglish
Pages (from-to)541-552
Number of pages12
JournalDevelopmental Cell
Volume30
Issue number5
DOIs
StatePublished - Sep 8 2014

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Vascular Endothelial Growth Factor A
Blood Vessels
Blood
Cytoprotection
Vascular Endothelium
Microvessels
Histamine
Retina
Permeability
Endothelial cells
Endothelial Cells
Brain
Lung
Chemical activation
Polarization
Tissue

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Hudson, N., Powner, M. B., Sarker, M. H., Burgoyne, T., Campbell, M., Ockrim, Z. K., ... Turowski, P. (2014). Differential apicobasal VEGF signaling at vascular blood-neural barriers. Developmental Cell, 30(5), 541-552. https://doi.org/10.1016/j.devcel.2014.06.027

Differential apicobasal VEGF signaling at vascular blood-neural barriers. / Hudson, Natalie; Powner, Michael B.; Sarker, Mosharraf H.; Burgoyne, Thomas; Campbell, Matthew; Ockrim, Zoe K.; Martinelli, Roberta; Futter, Clare E.; Grant, Maria B.; Fraser, Paul A.; Shima, David T.; Greenwood, John; Turowski, Patric.

In: Developmental Cell, Vol. 30, No. 5, 08.09.2014, p. 541-552.

Research output: Contribution to journalArticle

Hudson, N, Powner, MB, Sarker, MH, Burgoyne, T, Campbell, M, Ockrim, ZK, Martinelli, R, Futter, CE, Grant, MB, Fraser, PA, Shima, DT, Greenwood, J & Turowski, P 2014, 'Differential apicobasal VEGF signaling at vascular blood-neural barriers', Developmental Cell, vol. 30, no. 5, pp. 541-552. https://doi.org/10.1016/j.devcel.2014.06.027
Hudson N, Powner MB, Sarker MH, Burgoyne T, Campbell M, Ockrim ZK et al. Differential apicobasal VEGF signaling at vascular blood-neural barriers. Developmental Cell. 2014 Sep 8;30(5):541-552. https://doi.org/10.1016/j.devcel.2014.06.027
Hudson, Natalie ; Powner, Michael B. ; Sarker, Mosharraf H. ; Burgoyne, Thomas ; Campbell, Matthew ; Ockrim, Zoe K. ; Martinelli, Roberta ; Futter, Clare E. ; Grant, Maria B. ; Fraser, Paul A. ; Shima, David T. ; Greenwood, John ; Turowski, Patric. / Differential apicobasal VEGF signaling at vascular blood-neural barriers. In: Developmental Cell. 2014 ; Vol. 30, No. 5. pp. 541-552.
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