Stefan Liebner, Monica Corada, Thorsten Bangsow, Jane Babbage, Andrea Taddei, Cathrin Jacqueline Czupalla, Marco Reis, Angelina Felici, Hartwig Wolburg, Marcus Fruttiger, Makoto Mark Taketo, Harald von Melchner, Karl Plate, Holger Gerhardt, Elisabetta Dejana
- The blood–brain barrier (BBB) is confined to the endothelium of brain capillaries and is indispensable for fluid homeostasis and neuronal function. In this study, we show that endothelial Wnt/beta-catenin (beta-cat) signaling regulates induction and maintenance of BBB characteristics during embryonic and postnatal development. Endothelial specific stabilization of beta-cat in vivo enhances barrier maturation, whereas inactivation of beta-cat causes significant down-regulation of claudin3 (Cldn3), up-regulation of plamalemma vesicle-associated protein, and BBB breakdown. Stabilization of beta-cat in primary brain endothelial cells (ECs) in vitro by N-terminal truncation or Wnt3a treatment increases Cldn3 expression, BBB-type tight junction formation, and a BBB characteristic gene signature. Loss of beta-cat or inhibition of its signaling abrogates this effect. Furthermore, stabilization of beta-cat also increased Cldn3 and barrier properties in nonbrain-derived ECs. These findings may open new therapeutic avenues to modulate endothelial barrier function and to limit the devastating effects of BBB breakdown.
MetadatenAuthor: | Stefan LiebnerORCiDGND, Monica Corada, Thorsten Bangsow, Jane Babbage, Andrea Taddei, Cathrin Jacqueline CzupallaORCiDGND, Marco Reis, Angelina Felici, Hartwig Wolburg, Marcus Fruttiger, Makoto Mark Taketo, Harald von Melchner, Karl PlateGND, Holger Gerhardt, Elisabetta Dejana |
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URN: | urn:nbn:de:hebis:30-68153 |
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DOI: | https://doi.org/10.1083/jcb.200806024 |
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ISSN: | 1540-8140 |
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ISSN: | 0021-9525 |
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Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/18955553 |
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Parent Title (English): | The journal of cell biology |
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Publisher: | Rockefeller Univ. Press |
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Place of publication: | New York, NY |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2009/08/10 |
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Year of first Publication: | 2008 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2009/08/10 |
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Volume: | 183 |
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Issue: | 3 |
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Page Number: | 9 |
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First Page: | 409 |
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Last Page: | 417 |
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Note: | © 2008 Liebner et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
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HeBIS-PPN: | 21474972X |
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Institutes: | Medizin / Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Licence (German): | Creative Commons - Namensnennung-Keine kommerzielle Nutzung-Weitergabe unter gleichen Bedingungen |
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