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


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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Divisions: College of Health & Life Sciences
College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > School of Biosciences > Cellular and Molecular Biomedicine
College of Health & Life Sciences > Aston Medical School
Additional Information: © 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.
Uncontrolled Keywords: Agricultural and Biological Sciences(all),Biochemistry, Genetics and Molecular Biology(all),Medicine(all)
Publication ISSN: 1932-6203
Last Modified: 22 Feb 2024 08:08
Date Deposited: 18 Mar 2013 11:42
Full Text Link: http://www.plos ... al.pone.0018076
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2011-03-25
Authors: Cai, Jun
Wu, Lin
Qi, Xiaoping
Shaw, Lynn
Li Calzi, Sergio
Caballero, Sergio
Jiang, Wen G.
Vinores, Stanley A.
Antonetti, David
Ahmed, Asif (ORCID Profile 0000-0002-8755-8546)
Grant, Maria B.
Boulton, Michael E.



Version: Draft Version

License: Creative Commons Attribution

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