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FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature

Sabine, Amelie (författare)
CHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland.
Bovay, Esther (författare)
CHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland.
Demir, Cansaran Saygili (författare)
CHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland.
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Kimura, Wataru (författare)
Hamamatsu Univ Sch Med, Hamamatsu, Shizuoka 4313192, Japan.
Jaquet, Muriel (författare)
CHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland.
Agalarov, Yan (författare)
CHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland.
Zangger, Nadine (författare)
SIB, Lausanne, Switzerland.
Scallan, Joshua P. (författare)
Univ Missouri, Columbia, MO USA.
Graber, Werner (författare)
Univ Bern, Inst Anat, Bern, Switzerland.
Gulpinar, Elgin (författare)
Harvard Univ, Cambridge, MA USA.
Kwak, Brenda R. (författare)
Univ Geneva, Dept Pathol & Immunol, Geneva, Switzerland.;Univ Geneva, Dept Med Specializat Cardiol, Geneva, Switzerland.
Mäkinen, Taija (författare)
Uppsala universitet,Vaskulärbiologi
Martinez-Corral, Ines (författare)
Spanish Natl Canc Res Ctr, Madrid, Spain.
Ortega, Sagrario (författare)
Spanish Natl Canc Res Ctr, Madrid, Spain.
Delorenzi, Mauro (författare)
SIB, Lausanne, Switzerland.;Univ Lausanne, Ludwig Ctr Canc Res, Lausanne, Switzerland.
Kiefer, Friedemann (författare)
Max Planck Inst Mol Biomed, D-48149 Munster, Germany.
Davis, Michael J. (författare)
Univ Missouri, Columbia, MO USA.
Djonov, Valentin (författare)
Univ Bern, Inst Anat, Bern, Switzerland.
Miura, Naoyuld (författare)
Hamamatsu Univ Sch Med, Hamamatsu, Shizuoka 4313192, Japan.
Petrova, Tatiana V. (författare)
CHUV, Dept Fundamental Oncol, CH-1066 Epalinges, Switzerland.;Univ Lausanne, CH-1066 Epalinges, Switzerland.;Ecole Polytech Fed Lausanne, Swiss Canc Res Inst, Lausanne, Switzerland.
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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)
2015
2015
Engelska.
Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 125:10, s. 3861-3877
Relaterad länk:
https://urn.kb.se/re...
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https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

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