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

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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.

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Acknowledgements

This study was supported by a grant of the Deutsche Forschungsgemeinschaft (The SFB 487/B5).

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Authors and Affiliations

  1. Institute of Anatomy and Cell Biology, University of Würzburg, Koellikerstrasse 6, 97070, Würzburg, Germany

    Werner Baumgartner, Nikola Golenhofen, Agnes Weth & Detlev Drenckhahn

  2. Department of Developmental Biology, Max-Planck Institute of Immunobiology, Stuebeweg 51, 79108, Freiburg, Germany

    Takashi Hiiragi

  3. School of Science, Nottingham Trent University, Clifton Lane, Nottingham, NG11 8NS, UK

    Rob Saint & Martin Griffin

Authors
  1. Werner Baumgartner
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  2. Nikola Golenhofen
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  3. Agnes Weth
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  4. Takashi Hiiragi
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  5. Rob Saint
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  6. Martin Griffin
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  7. Detlev Drenckhahn
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Correspondence to Werner Baumgartner.

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Baumgartner, W., Golenhofen, N., Weth, A. et al. Role of transglutaminase 1 in stabilisation of intercellular junctions of the vascular endothelium. Histochem Cell Biol 122, 17–25 (2004). https://doi.org/10.1007/s00418-004-0668-y

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  • DOI: https://doi.org/10.1007/s00418-004-0668-y

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