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Endoglin prevents v...
Endoglin prevents vascular malformation by regulating flow-induced cell migration and specification through VEGFR2 signalling
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- Jin, Yi (författare)
- Uppsala universitet,Vaskulärbiologi,Karolinska Inst, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden.
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- Muhl, Lars (författare)
- Karolinska Institutet
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- Burmakin, Mikhail (författare)
- Karolinska Institutet
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- Wang, Yixin (författare)
- Karolinska Inst, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden.
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- Duchez, Anne-Claire (författare)
- Karolinska Inst, Dept Med Biochem & Biophys, Scheeles Vag 2, S-17177 Stockholm, Sweden.
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- Betsholtz, Christer (författare)
- Karolinska Institutet,Uppsala universitet,Vaskulärbiologi,Karolinska Inst, ICMC, Blickagangen 6, SE-14157 Huddinge, Sweden.
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- Arthur, Helen M. (författare)
- Newcastle Univ, Inst Med Genet, Int Ctr Life, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England.
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- Jakobsson, Lars (författare)
- Karolinska Institutet
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(creator_code:org_t)
- 2017-05-22
- 2017
- Engelska.
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Ingår i: Nature Cell Biology. - : NATURE PUBLISHING GROUP. - 1465-7392 .- 1476-4679. ; 19:6, s. 639-652
- Relaterad länk:
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https://europepmc.or...
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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
- Loss-of-function (LOF) mutations in the endothelial cell (EC)-enriched gene endoglin (ENG) cause the human disease hereditary haemorrhagic telangiectasia-1, characterized by vascular malformations promoted by vascular endothelial growth factor A (VEGFA). How ENG deficiency alters EC behaviour to trigger these anomalies is not understood. Mosaic ENG deletion in the postnatal mouse rendered Eng LOF ECs insensitive to flow-mediated venous to arterial migration. Eng LOF ECs retained within arterioles acquired venous characteristics and secondary ENG-independent proliferation resulting in arteriovenous malformation (AVM). Analysis following simultaneous Eng LOF and overexpression (OE) revealed that ENG OE ECs dominate tip-cell positions and home preferentially to arteries. ENG knockdown altered VEGFA-mediated VEGFR2 kinetics and promoted AKT signalling. Blockage of PI(3)K/AKT partly normalized flow-directed migration of ENG LOF ECs in vitro and reduced the severity of AVM in vivo. This demonstrates the requirement of ENG in flow-mediated migration and modulation of VEGFR2 signalling in vascular patterning.
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)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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