FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature.

Détails

Ressource 1Télécharger: JCI80454.pdf (10678.10 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_EAA65C411B89
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
FOXC2 and fluid shear stress stabilize postnatal lymphatic vasculature.
Périodique
Journal of Clinical Investigation
Auteur(s)
Sabine A., Bovay E., Demir C.S., Kimura W., Jaquet M., Agalarov Y., Zangger N., Scallan J.P., Graber W., Gulpinar E., Kwak B.R., Mäkinen T., Martinez-Corral I., Ortega S., Delorenzi M., Kiefer F., Davis M.J., Djonov V., Miura N., Petrova T.V.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
125
Numéro
10
Pages
3861-3877
Langue
anglais
Notes
Esther Bovay and Cansaran Saygili Demir contributed equally to this
work
Résumé
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.
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/10/2015 17:24
Dernière modification de la notice
20/08/2019 16:13
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