Sökning: WFRF:(Ramsköld Daniel)
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Disruption of the E...
Disruption of the Extracellular Matrix Progressively Impairs Central Nervous System Vascular Maturation Downstream of beta-Catenin Signaling
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- Jensen, Lasse (författare)
- Linköpings universitet,Linköping University,Avdelningen för kardiovaskulär medicin,Medicinska fakulteten,Region Östergötland, Klinisk farmakologi
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- Hot, Belma (författare)
- Karolinska Institute,Ludwig Institute for Cancer Research, Stockholm branch,Karolinska Inst, Sweden; Ludwig Inst Canc Res Ltd, Sweden
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- Ramsköld, Daniel (författare)
- Karolinska Institutet,Karolinska Institute,Ludwig Institute for Cancer Research, Stockholm branch,Karolinska Inst, Sweden; Ludwig Inst Canc Res Ltd, Sweden
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- Germano, Raoul F. V. (författare)
- Université Libre de Bruxelles (ULB),Univ Libre Bruxelles, Belgium
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- Yokota, Chika (författare)
- Stockholm University,Stockholms universitet,Institutionen för biokemi och biofysik,Ludwig Institute for Cancer Research Ltd, Sweden,Ludwig Institute for Cancer Research, Stockholm branch,Ludwig Inst Canc Res Ltd, Sweden; Stockholm Univ, Sweden
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- Giatrellis, Sarantis (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska Inst, Sweden
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- Lauschke, Volker M. (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska Inst, Sweden
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- Hubmacher, Dirk (författare)
- Icahn School of Medicine at Mount Sinai,Icahn Sch Med Mt Sinai, NY 10029 USA
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- Li, Minerva X. (författare)
- Lund University,Lunds universitet,LUBIN Lab- Lunds laboratorium för neurokirurgisk hjärnskadeforskning,Forskargrupper vid Lunds universitet,LUBIN Lab- Lund Brain Injury laboratory for Neurosurgical research,Lund University Research Groups,Ludwig Institute for Cancer Research, Stockholm branch,Ludwig Inst Canc Res Ltd, Sweden; Lund Univ, Sweden
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- Hupe, Mike (författare)
- Julius Maximilian University of Würzburg,Ludwig Institute for Cancer Research, Stockholm branch,Ludwig Inst Canc Res Ltd, Sweden; Univ Wurzburg, Germany
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- Arnold, Thomas D. (författare)
- University of California, San Francisco,Univ Calif San Francisco, CA 94143 USA
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- Sandberg, Rickard (författare)
- Karolinska Institutet,Karolinska Institute,Ludwig Institute for Cancer Research, Stockholm branch,Karolinska Inst, Sweden; Ludwig Inst Canc Res Ltd, Sweden
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- Frisén, Jonas (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska Inst, Sweden
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- Trusohamn, Marta (författare)
- Karolinska Institute,Karolinska Inst, Sweden
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- Martowicz, Agnieszka (författare)
- Karolinska Institute,Karolinska Inst, Sweden
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- Wisniewska-Kruk, Joanna (författare)
- Karolinska Institute,Karolinska Inst, Sweden
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- Nyqvist, Daniel (författare)
- Karolinska Institutet,Karolinska Institute,Karolinska Inst, Sweden
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- Adams, Ralf H. (författare)
- University of Münster,Univ Munster, Germany
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- Apte, Suneel S. (författare)
- Cleveland Clinic Foundation,Cleveland Clin Fdn, OH 44195 USA
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- Vanhollebeke, Benoit (författare)
- Walloon Excellence in Life Sciences and Biotechnology,Université Libre de Bruxelles (ULB),Univ Libre Bruxelles, Belgium; Walloon Excellence Life Sci and Biotechnol WELBIO, Belgium
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- Stenman, Jan M. (författare)
- Ludwig Institute for Cancer Research, Stockholm branch,Ludwig Inst Canc Res Ltd, Sweden
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- Kele, Julianna (författare)
- Karolinska Institutet,Karolinska Institute,Ludwig Institute for Cancer Research, Stockholm branch,Karolinska Inst, Sweden; Ludwig Inst Canc Res Ltd, Sweden
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(creator_code:org_t)
- LIPPINCOTT WILLIAMS & WILKINS, 2019
- 2019
- Engelska.
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - : LIPPINCOTT WILLIAMS & WILKINS. - 1079-5642 .- 1524-4636. ; 39:7, s. 1432-1447
- Relaterad länk:
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https://doi.org/10.1...
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http://dx.doi.org/10... (free)
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https://liu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Objective- The Wnt/beta-catenin pathway orchestrates development of the blood-brain barrier, but the downstream mechanisms involved at different developmental windows and in different central nervous system (CNS) tissues have remained elusive. Approach and Results- Here, we create a new mouse model allowing spatiotemporal investigations of Wnt/beta-catenin signaling by induced overexpression of Axin1, an inhibitor of beta-catenin signaling, specifically in endothelial cells (Axin1(iEC)-(OE)). AOE (Axin1 overexpression) in Axin1(iEC)-(OE) mice at stages following the initial vascular invasion of the CNS did not impair angiogenesis but led to premature vascular regression followed by progressive dilation and inhibition of vascular maturation resulting in forebrain-specific hemorrhage 4 days post-AOE. Analysis of the temporal Wnt/beta-catenin driven CNS vascular development in zebrafish also suggested that Axin1(iEC)-(OE) led to CNS vascular regression and impaired maturation but not inhibition of ongoing angiogenesis within the CNS. Transcriptomic profiling of isolated, beta-catenin signaling-deficient endothelial cells during early blood-brain barrier-development (E11.5) revealed ECM (extracellular matrix) proteins as one of the most severely deregulated clusters. Among the 20 genes constituting the forebrain endothelial cell-specific response signature, 8 (Adamtsl2, Apod, Ctsw, Htra3, Pglyrp1, Spock2, Ttyh2, and Wfdc1) encoded bona fide ECM proteins. This specific beta-catenin-responsive ECM signature was also repressed in Axin1(iEC)-(OE) and endothelial cell-specific beta-catenin-knockout mice (Ctnnb1-KOiEC) during initial blood-brain barrier maturation (E14.5), consistent with an important role of Wnt/beta-catenin signaling in orchestrating the development of the forebrain vascular ECM. Conclusions- These results suggest a novel mechanism of establishing a CNS endothelium-specific ECM signature downstream of Wnt-beta-catenin that impact spatiotemporally on blood-brain barrier differentiation during forebrain vessel development.
Ämnesord
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- basement membrane
- blood-brain barrier
- central nervous system
- embryonic development
- endothelial cells
- extracellular matrix
- vasculature
- basement membrane
- blood-brain barrier
- central nervous system
- embryonic development
- endothelial cells
- extracellular matrix
- vasculature
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Jensen, Lasse
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Hot, Belma
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Ramsköld, Daniel
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Germano, Raoul F ...
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Yokota, Chika
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Giatrellis, Sara ...
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visa fler...
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Lauschke, Volker ...
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Hubmacher, Dirk
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Li, Minerva X.
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Hupe, Mike
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Arnold, Thomas D ...
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Sandberg, Rickar ...
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Frisén, Jonas
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Trusohamn, Marta
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Martowicz, Agnie ...
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Wisniewska-Kruk, ...
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Nyqvist, Daniel
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Adams, Ralf H.
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Apte, Suneel S.
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Vanhollebeke, Be ...
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Stenman, Jan M.
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Kele, Julianna
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- Om ämnet
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- NATURVETENSKAP
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NATURVETENSKAP
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och Biologi
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Cell och molekyl ...
- Artiklar i publikationen
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Arteriosclerosis ...
- Av lärosätet
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Stockholms universitet
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Lunds universitet
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Linköpings universitet
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Karolinska Institutet