17 β‐estradiol transiently disrupts adherens junctions in endothelial cells
- 31 May 2005
- journal article
- fj express-summaries
- Published by Wiley in The FASEB Journal
- Vol. 19 (10), 1368-1370
- https://doi.org/10.1096/fj.04-2558fje
Abstract
Interendothelial junctions are important regulators of endothelial cell functions such as migration and proliferation, major features in angiogenesis, and endothelial cell monolayer wound healing. 17beta-estradiol regulates these functions in vivo and in vitro and also increases endothelial monolayer permeability as it results from impaired monolayer integrity and intercellular adhesion. We hypothesized that 17beta-estradiol affects these cell adhesion-dependent functions in endothelial cells by targeting the adherens junction complex. Here, we show that 17beta-estradiol increases uterine microvascular endothelial cell monolayer permeability and transiently redistributes interendothelial junction-forming proteins in endothelial cells. Concomitantly, adherens junction proteins are disconnected from the cytoskeleton and alpha-catenin, which links VE-cadherin to the cytoskeleton, is redistributed from the membrane and the adherens junction complex. Furthermore, 17beta-estradiol increased tyrosine phosphorylation of the adherens junction complex. These effects were inhibited by the estrogen receptor antagonist ICI 182,780 but could be provoked using non-cell membrane-permeable 17beta-estradiol-BSA in all cells tested, including EA.hy 926 cells, which have been shown unable to stimulate 17beta-estradiol-dependent gene transcription. Additionally, 17beta-estradiol treatment enhanced the angiogenic effect of vascular endothelial growth factor in an in vitro angiogenesis model, as a potential implication of the adherens junction disruption. Cotreatment with the Src-family kinase inhibitor PP2 prevented the redistribution and phosphorylation of the adherens junction proteins. Taken together, our data show that adherens junctions in endothelial cells are a downstream target of membrane-associated 17beta-estradiol signaling, possibly through Src-family kinases.Keywords
Funding Information
- National Heart, Lung, and Blood Institute (HL‐53918)
- Deutsche Forschungsgemeinschaft (GR1955/1‐1)
This publication has 58 references indexed in Scilit:
- p120 Catenin-Associated Fer and Fyn Tyrosine Kinases Regulate β-Catenin Tyr-142 Phosphorylation and β-Catenin-α-Catenin InteractionMolecular and Cellular Biology, 2003
- Truncated Estrogen Receptor α 46-kDa Isoform in Human Endothelial CellsCirculation, 2003
- A fluorescent resonant energy transfer–based biosensor reveals transient and regional myosin light chain kinase activation in lamella and cleavage furrowsThe Journal of cell biology, 2002
- Pores in the Sieve and Channels in the Wall: Control of Paracellular Permeability by Junctional Proteins in Endothelial CellsMicrocirculation, 2001
- Vascular Endothelial Growth Factor Induces Endothelial Fenestrations In VitroThe Journal of cell biology, 1998
- Protein-tyrosine Phosphatase-mediated Decrease of Epidermal Growth Factor and Platelet-derived Growth Factor Receptor Tyrosine Phosphorylation in High Cell Density CulturesPublished by Elsevier ,1996
- Cell Adhesion: The Molecular Basis of Tissue Architecture and MorphogenesisCell, 1996
- Discovery of a Novel, Potent, and Src Family-selective Tyrosine Kinase InhibitorJournal of Biological Chemistry, 1996
- Functional Properties of Human Vascular Endothelial Cadherin (7B4/Cadherin-5), an Endothelium-Specific CadherinArteriosclerosis, Thrombosis, and Vascular Biology, 1995
- The molecular organization of endothelial cell to cell junctions: differential association of plakoglobin, beta-catenin, and alpha-catenin with vascular endothelial cadherin (VE-cadherin).The Journal of cell biology, 1995