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  • Sabine, AmelieCHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland. (författare)

FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature

  • Artikel/kapitelEngelska2015

Förlag, utgivningsår, omfång ...

  • 2015
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-265686
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-265686URI
  • https://doi.org/10.1172/JCI80454DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Biomechanical forces, such as fluid shear stress, govern multiple aspects of endothelial cell biology. In blood vessels, disturbed flow is associated with vascular diseases, such as atherosclerosis, and promotes endothelial cell proliferation and apoptosis. Here, we identified an important role for disturbed flow in lymphatic vessels, in which it cooperates with the transcription factor FOXC2 to ensure lifelong stability of the lymphatic vasculature. In cultured lymphatic endothelial cells, FOXC2 inactivation conferred abnormal shear stress sensing, promoting junction disassembly and entry into the cell cycle. Loss of FOXC2-dependent quiescence was mediated by the Hippo pathway transcriptional coactivator TAZ and, ultimately, led to cell death. In murine models, inducible deletion of Foxc2 within the lymphatic vasculature led to cell-cell junction defects, regression of valves, and focal vascular lumen collapse, which triggered generalized lymphatic vascular dysfunction and lethality. Together, our work describes a fundamental mechanism by which FOXC2 and oscillatory shear stress maintain lymphatic endothelial cell quiescence through intercellular junction and cytoskeleton stabilization and provides an essential link between biomechanical forces and endothelial cell identity that is necessary for postnatal vessel homeostasis. As FOXC2 is mutated in lymphedema-distichiasis syndrome, our data also underscore the role of impaired mechanotransduction in the pathology of this hereditary human disease.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Bovay, EstherCHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland. (författare)
  • Demir, Cansaran SaygiliCHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland. (författare)
  • Kimura, WataruHamamatsu Univ Sch Med, Hamamatsu, Shizuoka 4313192, Japan. (författare)
  • Jaquet, MurielCHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland. (författare)
  • Agalarov, YanCHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland. (författare)
  • Zangger, NadineSIB, Lausanne, Switzerland. (författare)
  • Scallan, Joshua P.Univ Missouri, Columbia, MO USA. (författare)
  • Graber, WernerUniv Bern, Inst Anat, Bern, Switzerland. (författare)
  • Gulpinar, ElginHarvard Univ, Cambridge, MA USA. (författare)
  • Kwak, Brenda R.Univ Geneva, Dept Pathol & Immunol, Geneva, Switzerland.;Univ Geneva, Dept Med Specializat Cardiol, Geneva, Switzerland. (författare)
  • Mäkinen, TaijaUppsala universitet,Vaskulärbiologi(Swepub:uu)taima352 (författare)
  • Martinez-Corral, InesSpanish Natl Canc Res Ctr, Madrid, Spain. (författare)
  • Ortega, SagrarioSpanish Natl Canc Res Ctr, Madrid, Spain. (författare)
  • Delorenzi, MauroSIB, Lausanne, Switzerland.;Univ Lausanne, Ludwig Ctr Canc Res, Lausanne, Switzerland. (författare)
  • Kiefer, FriedemannMax Planck Inst Mol Biomed, D-48149 Munster, Germany. (författare)
  • Davis, Michael J.Univ Missouri, Columbia, MO USA. (författare)
  • Djonov, ValentinUniv Bern, Inst Anat, Bern, Switzerland. (författare)
  • Miura, NaoyuldHamamatsu Univ Sch Med, Hamamatsu, Shizuoka 4313192, Japan. (författare)
  • Petrova, Tatiana V.CHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland.;Ecole Polytech Fed Lausanne, Swiss Canc Res Inst, Lausanne, Switzerland. (författare)
  • CHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland.Hamamatsu Univ Sch Med, Hamamatsu, Shizuoka 4313192, Japan. (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Journal of Clinical Investigation125:10, s. 3861-38770021-97381558-8238

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