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Endothelial beta-Ca...
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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- Martowicz, Agnieszka (author)
- Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, Biomedicum 6D, S-17165 Stockholm, Sweden
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- Trusohamn, Marta (author)
- Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, Biomedicum 6D, S-17165 Stockholm, Sweden
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- Jensen, Nina (author)
- Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, Biomedicum 6D, S-17165 Stockholm, Sweden
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- Wisniewska-Kruk, Joanna (author)
- Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, Biomedicum 6D, S-17165 Stockholm, Sweden
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- Corada, Monica (author)
- FIRC Inst Mol Oncol, IFOM, Milan, Italy
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- Ning, Frank Chenfei (author)
- Karolinska Institutet
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- Kele, Julianna (author)
- Karolinska Institutet
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- Dejana, Elisabetta (author)
- Uppsala universitet,Vaskulärbiologi,FIRC Inst Mol Oncol, IFOM, Milan, Italy
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- Nyqvist, Daniel (author)
- Karolinska Institutet
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(creator_code:org_t)
- LIPPINCOTT WILLIAMS & WILKINS, 2019
- 2019
- English.
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In: Arteriosclerosis, Thrombosis and Vascular Biology. - : LIPPINCOTT WILLIAMS & WILKINS. - 1079-5642 .- 1524-4636. ; 39:11, s. 2273-2288
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- beta catenin
- blood-brain barrier
- central nervous system
- endothelial cell
- vegf
Publication and Content Type
- ref (subject category)
- art (subject category)
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