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Endothelial beta-Ca...
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Martowicz, AgnieszkaKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, Biomedicum 6D, S-17165 Stockholm, Sweden
(author)
Endothelial beta-Catenin Signaling Supports Postnatal Brain and Retinal Angiogenesis by Promoting Sprouting, Tip Cell Formation, and VEGFR (Vascular Endothelial Growth Factor Receptor) 2 Expression
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LIPPINCOTT WILLIAMS & WILKINS,2019
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LIBRIS-ID:oai:DiVA.org:uu-397792
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-397792URI
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https://doi.org/10.1161/ATVBAHA.119.312749DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:142245153URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Objective: Activation of endothelial beta-catenin signaling by neural cell-derived Norrin or Wnt ligands is vital for the vascularization of the retina and brain. Mutations in members of the Norrin/beta-catenin pathway contribute to inherited blinding disorders because of defective vascular development and dysfunctional blood-retina barrier. Despite a vital role for endothelial beta-catenin signaling in central nervous system health and disease, its contribution to central nervous system angiogenesis and its interactions with downstream signaling cascades remains incompletely understood.Approach and Results: Here, using genetically modified mouse models, we show that impaired endothelial beta-catenin signaling caused hypovascularization of the postnatal retina and brain because of deficient endothelial cell proliferation and sprouting. Mosaic genetic analysis demonstrated that endothelial beta-catenin promotes but is not required for tip cell formation. In addition, pharmacological treatment revealed that angiogenesis under conditions of inhibited Notch signaling depends upon endothelial beta-catenin. Importantly, impaired endothelial beta-catenin signaling abrogated the expression of the VEGFR (vascular endothelial growth factor receptor)-2 and VEGFR3 in brain microvessels but not in the lung endothelium.Conclusions: Our study identifies molecular crosstalk between the Wnt/beta-catenin and the Notch and VEGF-A signaling pathways and strongly suggest that endothelial beta-catenin signaling supports central nervous system angiogenesis by promoting endothelial cell sprouting, tip cell formation, and VEGF-A/VEGFR2 signaling.
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Trusohamn, MartaKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, Biomedicum 6D, S-17165 Stockholm, Sweden
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Jensen, NinaKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, Biomedicum 6D, S-17165 Stockholm, Sweden
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Wisniewska-Kruk, JoannaKarolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, Biomedicum 6D, S-17165 Stockholm, Sweden
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Corada, MonicaFIRC Inst Mol Oncol, IFOM, Milan, Italy
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Ning, Frank ChenfeiKarolinska Institutet
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Kele, JuliannaKarolinska Institutet
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Dejana, ElisabettaUppsala universitet,Vaskulärbiologi,FIRC Inst Mol Oncol, IFOM, Milan, Italy(Swepub:uu)elide443
(author)
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Nyqvist, DanielKarolinska Institutet
(author)
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Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, Biomedicum 6D, S-17165 Stockholm, SwedenFIRC Inst Mol Oncol, IFOM, Milan, Italy
(creator_code:org_t)
Related titles
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In:Arteriosclerosis, Thrombosis and Vascular Biology: LIPPINCOTT WILLIAMS & WILKINS39:11, s. 2273-22881079-56421524-4636
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