Role of transglutaminase 1 in stabilisation of intercellular junctions of the vascular endothelium

Werner Baumgartner, Nikola Golenhofen, Agnes Weth, Takashi Hiiragi, Rob Saint, Martin Griffin, Detlev Drenckhahn

Research output: Contribution to journalArticle

Abstract

Microvascular endothelial monolayers from mouse myocardium (MyEnd) cultured for up to 5 days postconfluency became increasingly resistant to various barrier-compromising stimuli such as low extracellular Ca2+ and treatment with the Ca2+ ionophore A23187 and with the actin depolymerising compound cytochalasin D. In contrast, microvascular endothelial monolayers from mouse lung microvessels (PulmEnd) remained sensitive to these conditions during the entire culture period which corresponds to the well-known in vivo sensitivity of the lung microvasculature to Ca2+depletion and cytochalasin D treatment. One molecular difference between pulmonary and myocardial endothelial cells was found to be transglutaminase 1 (TGase1) which is strongly expressed in myocardial endothelial cells but is absent from pulmonary endothelial cells. Resistance of MyEnd cells to barrier-breaking conditions correlated strongly with translocation of TGase1 to intercellular junctions. Simultaneous inhibition of intracellular and extracellular TGase activity by monodansylcadaverine (MDC) strongly weakened barrier properties of MyEnd monolayers, whereas inhibition of extracellular TGases by the membrane-impermeable active site-directed TGase inhibitor R281 did not reduce barrier properties. Weakening of barrier properties could be also induced in MyEnd cells by downregulation of TGase1 expression using RNAi-based gene silencing. These findings suggest that crosslinking activity of intracellular TGase1 at intercellular junctions may play a role in controlling barrier properties of endothelial monolayers.

Original languageEnglish
Pages (from-to)17-25
Number of pages9
JournalHistochemistry and Cell Biology
Volume122
Issue number1
Early online date25 Jun 2004
DOIs
Publication statusPublished - Jul 2004

Keywords

  • VE-cadherin
  • permeability
  • cell adhesion
  • TGaseK
  • TGase1
  • RNAi

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