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Endothelial Unc5B c...
Endothelial Unc5B controls blood-brain barrier integrity
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- Boye, Kevin (författare)
- Yale Univ, Sch Med, Dept Internal Med, Cardiovasc Res Ctr, New Haven, CT 06510 USA.
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- Geraldo, Luiz Henrique (författare)
- Yale Univ, Sch Med, Dept Internal Med, Cardiovasc Res Ctr, New Haven, CT 06510 USA.;Univ Paris, PARCC, INSERM, F-75015 Paris, France.
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- Furtado, Jessica (författare)
- Yale Univ, Sch Med, Dept Internal Med, Cardiovasc Res Ctr, New Haven, CT 06510 USA.
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- Pibouin-Fragner, Laurence (författare)
- Univ Paris, PARCC, INSERM, F-75015 Paris, France.
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- Poulet, Mathilde (författare)
- Yale Univ, Sch Med, Dept Internal Med, Cardiovasc Res Ctr, New Haven, CT 06510 USA.;Univ Paris, PARCC, INSERM, F-75015 Paris, France.
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- Kim, Doyeun (författare)
- OliX Pharmaceut, Suwon, South Korea.
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- Nelson, Bryce (författare)
- Yale Univ, Sch Med, Dept Pharmacol, Canc Biol Inst, New Haven, CT 06510 USA.
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- Xu, Yunling (författare)
- Univ Paris, PARCC, INSERM, F-75015 Paris, France.
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- Jacob, Laurent (författare)
- Univ Paris, PARCC, INSERM, F-75015 Paris, France.
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- Maissa, Nawal (författare)
- Univ Paris, PARCC, INSERM, F-75015 Paris, France.
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- Agalliu, Dritan (författare)
- Columbia Univ, Dept Neurol, Irving Med Ctr, New York, NY USA.;Columbia Univ, Dept Pathol & Cell Biol, Irving Med Ctr, New York, NY USA.
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- Claesson-Welsh, Lena (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Ackerman, Susan L. (författare)
- Univ Calif San Diego, Div Biol Sci, Sect Neurobiol, La Jolla, CA 92093 USA.;Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.;Howard Hughes Med Inst, La Jolla, CA USA.
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- Eichmann, Anne (författare)
- Yale Univ, Sch Med, Dept Internal Med, Cardiovasc Res Ctr, New Haven, CT 06510 USA.;Univ Paris, PARCC, INSERM, F-75015 Paris, France.;Yale Univ, Sch Med, Dept Mol & Cellular Physiol, New Haven, CT 06520 USA.
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Yale Univ, Sch Med, Dept Internal Med, Cardiovasc Res Ctr, New Haven, CT 06510 USA Yale Univ, Sch Med, Dept Internal Med, Cardiovasc Res Ctr, New Haven, CT 06510 USA.;Univ Paris, PARCC, INSERM, F-75015 Paris, France. (creator_code:org_t)
- 2022-03-04
- 2022
- Engelska.
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The authors show that Netrin-1-Unc5B signaling controls blood-brain barrier integrity by maintaining Wnt/b-catenin signaling and that delivery of antibodies blocking Netrin-1 binding to Unc5B causes transient and size-selective BBB breakdown. Blood-brain barrier (BBB) integrity is critical for proper function of the central nervous system (CNS). Here, we show that the endothelial Unc5B receptor controls BBB integrity by maintaining Wnt/beta-catenin signaling. Inducible endothelial-specific deletion of Unc5B in adult mice leads to BBB leak from brain capillaries that convert to a barrier-incompetent state with reduced Claudin-5 and increased PLVAP expression. Loss of Unc5B decreases BBB Wnt/beta-catenin signaling, and beta-catenin overexpression rescues Unc5B mutant BBB defects. Mechanistically, the Unc5B ligand Netrin-1 enhances Unc5B interaction with the Wnt co-receptor LRP6, induces its phosphorylation and activates Wnt/beta-catenin downstream signaling. Intravenous delivery of antibodies blocking Netrin-1 binding to Unc5B causes a transient BBB breakdown and disruption of Wnt signaling, followed by neurovascular barrier resealing. These data identify Netrin-1-Unc5B signaling as a ligand-receptor pathway that regulates BBB integrity, with implications for CNS diseases.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Boye, Kevin
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Geraldo, Luiz He ...
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Furtado, Jessica
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Pibouin-Fragner, ...
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Poulet, Mathilde
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Kim, Doyeun
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visa fler...
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Nelson, Bryce
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Xu, Yunling
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Jacob, Laurent
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Maissa, Nawal
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Agalliu, Dritan
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Claesson-Welsh, ...
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Ackerman, Susan ...
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Eichmann, Anne
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visa färre...
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