Thrombin induces rapid disassembly of claudin-5 from the tight junction of endothelial cells.
The cell-to-cell junction of endothelial cells (ECs) regulates the fence function of the vascular system. Previously we showed that ECs derived from embryonic stem cells (i.e., EECs) develop to form stable endothelial sheets in monolayer cultures. Immunohistochemical analysis revealed that these EECs formed intercellular junctions with the help of vascular endothelial cadherin (VECD) and claudin-5. In this study, we investigated the response of EC sheets to stimuli that are known to increase vascular permeability. While vascular endothelial growth factor A and histamine disrupted the EC junction by enhancing contraction of EECs, thrombin affected specifically the localization of claudin-5 at this junction. We could not detect any significant effect of thrombin on the localization of VECD. Concerning thrombin receptors, EECs expressed protease-activated receptor 1 (PAR1) but not PAR4. Consistent with this expression pattern, PAR1 agonists eliminated claudin-5 as effectively as thrombin itself. This is the first report to show that claudin-5 can be disassembled from the EC junction in a signal-dependent manner and to suggest that claudin-5 mobilization is a cause of PAR1-induced increase in vascular permeability.
Kondo
Nobuyuki
N
Stem Cell Biology Laboratory, Center for Developmental Biology, Riken, Kobe, Japan. kondon@hyo-med.ac.jp
Ogawa
Minetaro
M
Wada
Hiromi
H
Nishikawa
Shin-Ichi
S
D000818:Animals; D000911:Antibodies, Monoclonal; D015820:Cadherins / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D062507:Claudin-5; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013917:Thrombin / Q000494:pharmacology*; D019108:Tight Junctions / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology
D000911:Antibodies, Monoclonal; C107466:CLDN5 protein, human; D015820:Cadherins; D062507:Claudin-5; D008565:Membrane Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2; D013917:Thrombin