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

33 Scopus citations

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 (US)
Article numbere18076
JournalPloS one
Volume6
Issue number3
DOIs
StatePublished - Jan 1 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Cai, J., Wu, L., Qi, X., Shaw, L., Li Calzi, S., Caballero, S., Jiang, W. G., Vinores, S. A., Antonetti, D., Ahmed, A., Grant, M. B., & Boulton, M. E. (2011). Placenta growth factor-1 exerts time-dependent stabilization of adherens junctions following VEGF-induced vascular permeability. PloS one, 6(3), [e18076]. https://doi.org/10.1371/journal.pone.0018076