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Placenta growth factor-1 exerts time-dependent stabilization of adherens junctions following VEGF-induced vascular permeability.
- Source :
-
PloS one [PLoS One] 2011 Mar 25; Vol. 6 (3), pp. e18076. Date of Electronic Publication: 2011 Mar 25. - Publication Year :
- 2011
-
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.
- Subjects :
- Animals
Antigens, CD genetics
Base Sequence
Cadherins genetics
Claudins metabolism
Humans
Mice
Molecular Sequence Data
Phosphorylation drug effects
Placenta Growth Factor
Promoter Regions, Genetic genetics
Protein Binding drug effects
Sp1 Transcription Factor metabolism
Sp3 Transcription Factor metabolism
Tight Junctions drug effects
Tight Junctions metabolism
Time Factors
Transcriptional Activation drug effects
Vascular Endothelial Growth Factor Receptor-1 metabolism
Vascular Endothelial Growth Factor Receptor-2 metabolism
Adherens Junctions drug effects
Adherens Junctions metabolism
Capillary Permeability drug effects
Pregnancy Proteins pharmacology
Vascular Endothelial Growth Factor A pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 6
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 21464949
- Full Text :
- https://doi.org/10.1371/journal.pone.0018076