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Identification of I...
Identification of ILK as a critical regulator of VEGFR3 signalling and lymphatic vascular growth
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- Urner, Sofia (author)
- Heinrich Heine Univ Dusseldorf, Inst Metab Physiol, Dusseldorf, Germany
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- Planas-Paz, Lara (author)
- Heinrich Heine Univ Dusseldorf, Inst Metab Physiol, Dusseldorf, Germany
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- Hilger, Laura Sophie (author)
- Heinrich Heine Univ Dusseldorf, Inst Metab Physiol, Dusseldorf, Germany
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- Henning, Carina (author)
- Heinrich Heine Univ Dusseldorf, Inst Metab Physiol, Dusseldorf, Germany
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- Branopolski, Anna (author)
- Heinrich Heine Univ Dusseldorf, Inst Metab Physiol, Dusseldorf, Germany;Heinrich Heine Univ Dusseldorf, Med Fac, Div Cardiol Pulmonol & Vasc Med, Dusseldorf, Germany
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- Kelly-Goss, Molly (author)
- Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA
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- Stanczuk, Lukas (author)
- Uppsala universitet,Vaskulärbiologi
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- Pitter, Bettina (author)
- Ludwig Maximilians Univ Munchen, Univ Hosp, Walter Brendel Ctr Expt Med, Munich, Germany
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- Montanez, Eloi (author)
- Ludwig Maximilians Univ Munchen, Univ Hosp, Walter Brendel Ctr Expt Med, Munich, Germany
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- Peirce, Shayn M. (author)
- Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA
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- Mäkinen, Taija (author)
- Uppsala universitet,Vaskulärbiologi
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- Lammert, Eckhard (author)
- Heinrich Heine Univ Dusseldorf, Inst Metab Physiol, Dusseldorf, Germany;Heine Univ Dusseldorf, Leibniz Ctr Diabet Res Heinrich, German Diabet Ctr DDZ, Inst Beta Cell Biol, Dusseldorf, Germany;German Ctr Diabet Res DZD eV, Neuherberg, Germany
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(creator_code:org_t)
- 2018-12-05
- 2019
- English.
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In: EMBO Journal. - : WILEY. - 0261-4189 .- 1460-2075. ; 38:2
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Vascular endothelial growth factor receptor-3 (VEGFR3) signalling promotes lymphangiogenesis. While there are many reported mechanisms of VEGFR3 activation, there is little understanding of how VEGFR3 signalling is attenuated to prevent lymphatic vascular overgrowth and ensure proper lymph vessel development. Here, we show that endothelial cell-specific depletion of integrin-linked kinase (ILK) in mouse embryos hyper-activates VEGFR3 signalling and leads to overgrowth of the jugular lymph sacs/primordial thoracic ducts, oedema and embryonic lethality. Lymphatic endothelial cell (LEC)-specific deletion of Ilk in adult mice initiates lymphatic vascular expansion in different organs, including cornea, skin and myocardium. Knockdown of ILK in human LECs triggers VEGFR3 tyrosine phosphorylation and proliferation. ILK is further found to impede interactions between VEGFR3 and beta 1 integrin in vitro and in vivo, and endothelial cell-specific deletion of an Itgb1 allele rescues the excessive lymphatic vascular growth observed upon ILK depletion. Finally, mechanical stimulation disrupts the assembly of ILK and beta 1 integrin, releasing the integrin to enable its interaction with VEGFR3. Our data suggest that ILK facilitates mechanically regulated VEGFR3 signalling via controlling its interaction with beta 1 integrin and thus ensures proper development of lymphatic vessels.
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
- integrin-linked kinase
- lymphatic vasculature
- mechanical stimulation
- VEGFR3
- beta 1 integrin
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Urner, Sofia
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Planas-Paz, Lara
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Hilger, Laura So ...
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Henning, Carina
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Branopolski, Ann ...
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Kelly-Goss, Moll ...
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show more...
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Stanczuk, Lukas
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Pitter, Bettina
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Montanez, Eloi
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Peirce, Shayn M.
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Mäkinen, Taija
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Lammert, Eckhard
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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EMBO Journal
- By the university
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Uppsala University