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| Content Provider | PubMed Central |
|---|---|
| Author | Cai, Jun Wu, Lin Qi, Xiaoping Shaw, Lynn Calzi, Sergio Li Caballero, Sergio Jiang, Wen G. Vinores, Stanley A. Antonetti, David Ahmed, Asif Grant, Maria B. Boulton, Michael E. |
| Editor | Fadini, Gian Paolo |
| 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. |
| Related Links | http://dx.doi.org/10.1371/journal.pone.0018076 |
| Starting Page | 18076 |
| File Format | |
| ISSN | 19326203 |
| e-ISSN | 19326203 |
| Journal | PLoS ONE |
| Issue Number | 3 |
| Volume Number | 6 |
| Language | English |
| Publisher | Public Library of Science |
| Publisher Date | 2011-03-25 |
| Access Restriction | Open |
| Rights Holder | Public Library of Science |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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