Premium
17 β‐estradiol transiently disrupts adherens junctions in endothelial cells
Author(s) -
Groten Tanja,
Pierce Amy A.,
Huen Arthur C.,
Schnaper H. William
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2558fje
Subject(s) - adherens junction , microbiology and biotechnology , biology , endothelial stem cell , cell junction , s1pr1 , angiogenesis , tight junction , vascular endothelial growth factor a , cadherin , cancer research , cell , vascular endothelial growth factor , biochemistry , in vitro , vegf receptors
Interendothelial junctions are important regulators of endothelial cell functions such as migration and proliferation, major features in angiogenesis, and endothelial cell monolayer wound healing. 17β‐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 17β‐estradiol affects these cell adhesion‐dependent functions in endothelial cells by targeting the adherens junction complex. Here, we show that 17β‐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 α‐catenin, which links VE‐cadherin to the cytoskeleton, is redistributed from the membrane and the adherens junction complex. Furthermore, 17β‐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 17β‐estradiol‐BSA in all cells tested, including EA.hy 926 cells, which have been shown unable to stimulate 17β‐estradiol‐dependent gene transcription. Additionally, 17β‐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 17β‐estradiol signaling, possibly through Src‐family kinases.