Placenta growth factor-1 exerts time-dependent stabilization of adherens junctions following VEGF-induced vascular permeability

Jun Cai, Lin Wu, Xiaoping Qi, Lynn Shaw, Sergio Li Calzi, Sergio Caballero, Wen G. Jiang, Stanley A. Vinores, David Antonetti, Asif Ahmed, Maria B. Grant, Michael E. Boulton

Research output: Contribution to journalArticle

Abstract

Increased vascular permeability is an early event characteristic of tissue ischemia and angiogenesis. Although VEGF family members are potent promoters of endothelial permeability the role of placental growth factor (PlGF) is hotly debated. Here we investigated PlGF isoforms 1 and 2 and present in vitro and in vivo evidence that PlGF-1, but not PlGF-2, can inhibit VEGF-induced permeability but only during a critical window post-VEGF exposure. PlGF-1 promotes VE-cadherin expression via the trans-activating Sp1 and Sp3 interaction with the VE-cadherin promoter and subsequently stabilizes transendothelial junctions, but only after activation of endothelial cells by VEGF. PlGF-1 regulates vascular permeability associated with the rapid localization of VE-cadherin to the plasma membrane and dephosphorylation of tyrosine residues that precedes changes observed in claudin 5 tyrosine phosphorylation and membrane localization. The critical window during which PlGF-1 exerts its effect on VEGF-induced permeability highlights the importance of the translational significance of this work in that PLGF-1 likely serves as an endogenous anti-permeability factor whose effectiveness is limited to a precise time point following vascular injury. Clinical approaches that would pattern nature's approach would thus limit treatments to precise intervals following injury and bring attention to use of agents only during therapeutic windows.
Original languageEnglish
Article numbere18076
Number of pages16
JournalPLoS ONE
Volume6
Issue number3
DOIs
Publication statusPublished - 25 Mar 2011

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Adherens Junctions
Capillary Permeability
placenta
blood vessels
growth factors
Vascular Endothelial Growth Factor A
Intercellular Signaling Peptides and Proteins
permeability
Stabilization
cadherins
Permeability
Tyrosine
tyrosine
Claudin-5
Phosphorylation
dephosphorylation
Vascular System Injuries
Endothelial cells
Cell membranes
ischemia

Bibliographical note

© 2011 Cai et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cite this

Cai, Jun ; Wu, Lin ; Qi, Xiaoping ; Shaw, Lynn ; Li Calzi, Sergio ; Caballero, Sergio ; Jiang, Wen G. ; Vinores, Stanley A. ; Antonetti, David ; Ahmed, Asif ; Grant, Maria B. ; Boulton, Michael E. / Placenta growth factor-1 exerts time-dependent stabilization of adherens junctions following VEGF-induced vascular permeability. In: PLoS ONE. 2011 ; Vol. 6, No. 3.
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Cai, J, Wu, L, Qi, X, Shaw, L, Li Calzi, S, Caballero, S, Jiang, WG, Vinores, SA, Antonetti, D, Ahmed, A, Grant, MB & Boulton, ME 2011, 'Placenta growth factor-1 exerts time-dependent stabilization of adherens junctions following VEGF-induced vascular permeability', PLoS ONE, vol. 6, no. 3, e18076. https://doi.org/10.1371/journal.pone.0018076

Placenta growth factor-1 exerts time-dependent stabilization of adherens junctions following VEGF-induced vascular permeability. / Cai, Jun; Wu, Lin; Qi, Xiaoping; Shaw, Lynn; Li Calzi, Sergio; Caballero, Sergio; Jiang, Wen G.; Vinores, Stanley A.; Antonetti, David; Ahmed, Asif; Grant, Maria B.; Boulton, Michael E.

In: PLoS ONE, Vol. 6, No. 3, e18076, 25.03.2011.

Research output: Contribution to journalArticle

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AU - Cai, Jun

AU - Wu, Lin

AU - Qi, Xiaoping

AU - Shaw, Lynn

AU - Li Calzi, Sergio

AU - Caballero, Sergio

AU - Jiang, Wen G.

AU - Vinores, Stanley A.

AU - Antonetti, David

AU - Ahmed, Asif

AU - Grant, Maria B.

AU - Boulton, Michael E.

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N2 - Increased vascular permeability is an early event characteristic of tissue ischemia and angiogenesis. Although VEGF family members are potent promoters of endothelial permeability the role of placental growth factor (PlGF) is hotly debated. Here we investigated PlGF isoforms 1 and 2 and present in vitro and in vivo evidence that PlGF-1, but not PlGF-2, can inhibit VEGF-induced permeability but only during a critical window post-VEGF exposure. PlGF-1 promotes VE-cadherin expression via the trans-activating Sp1 and Sp3 interaction with the VE-cadherin promoter and subsequently stabilizes transendothelial junctions, but only after activation of endothelial cells by VEGF. PlGF-1 regulates vascular permeability associated with the rapid localization of VE-cadherin to the plasma membrane and dephosphorylation of tyrosine residues that precedes changes observed in claudin 5 tyrosine phosphorylation and membrane localization. The critical window during which PlGF-1 exerts its effect on VEGF-induced permeability highlights the importance of the translational significance of this work in that PLGF-1 likely serves as an endogenous anti-permeability factor whose effectiveness is limited to a precise time point following vascular injury. Clinical approaches that would pattern nature's approach would thus limit treatments to precise intervals following injury and bring attention to use of agents only during therapeutic windows.

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