title: Frizzled7 controls vascular permeability through the Wnt-canonical pathway and cross-talk with endothelial cell junction complexes.
abstract: OBJECTIVE
  Vascular permeability is essential for the health of normal tissues and is an important characteristic of many disease states. The role of the Wnt/frizzled pathway in vascular biology has recently been reported. The objectives of this study are to analyse the role of Frizzled7 (Fzd7) receptor in the control of vascular integrity.
  
  
  RESULTS
  Fzd7 is expressed in endothelial cells and accumulates at the points of cell-cell contact in association with VE-cadherin and β-catenin, two major adherens junction molecules. To selectively delete fzd7 in the vasculature, we developed gene targeting approaches using CreLox strategy in mice. Genetic fzd7 inhibition in the endothelium increases vascular permeability in basal and factor-induced conditions. On the cellular level, fzd7 knockdown or depletion leads to an increase in paracellular permeability with a loss of adherens junction organization. These impairments are associated with a decrease in both VE-Cadherin and β-catenin expression, a decrease in their association and an increase of tyrosine phosphorylation of VE-cadherin/β-catenin. Fzd7 transduces a Wnt/β-catenin signalling cascade that is required to regulate β-catenin and canonical target gene expression. Finally, LiCl, a GSK3 inhibitor, and β-catenin overexpression rescued endothelial integrity and adherens junction organization, induced by fzd7 deletion.
  
  
  CONCLUSIONS
  These findings establish that Fzd7 is a new partner of adherens junctional complex and represents a novel molecular switch for the control of vascular permeability via activation of the Wnt-canonical pathway.
authors.affiliation: Adaptation cardiovasculaire à l'ischémie, INSERM U1034, 125 Avenue du Haut Lévèque, 33 600 Pessac, France Adaptation cardiovasculaire à l'ischémie, Bordeaux University, U1034, Pessac, France Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: Ferreira Tojais
authors.affiliation: Adaptation cardiovasculaire à l'ischémie, INSERM U1034, 125 Avenue du Haut Lévèque, 33 600 Pessac, France Adaptation cardiovasculaire à l'ischémie, Bordeaux University, U1034, Pessac, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Peghaire
authors.affiliation: Adaptation cardiovasculaire à l'ischémie, INSERM U1034, 125 Avenue du Haut Lévèque, 33 600 Pessac, France Adaptation cardiovasculaire à l'ischémie, Bordeaux University, U1034, Pessac, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Franzl
authors.affiliation: Adaptation cardiovasculaire à l'ischémie, INSERM U1034, 125 Avenue du Haut Lévèque, 33 600 Pessac, France Adaptation cardiovasculaire à l'ischémie, Bordeaux University, U1034, Pessac, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Larrieu-Lahargue
authors.affiliation: Adaptation cardiovasculaire à l'ischémie, INSERM U1034, 125 Avenue du Haut Lévèque, 33 600 Pessac, France Adaptation cardiovasculaire à l'ischémie, Bordeaux University, U1034, Pessac, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Jaspard
authors.affiliation: Adaptation cardiovasculaire à l'ischémie, INSERM U1034, 125 Avenue du Haut Lévèque, 33 600 Pessac, France Adaptation cardiovasculaire à l'ischémie, Bordeaux University, U1034, Pessac, France.
authors.forename: Annabelle
authors.initials: A
authors.lastname: Reynaud
authors.affiliation: Adaptation cardiovasculaire à l'ischémie, INSERM U1034, 125 Avenue du Haut Lévèque, 33 600 Pessac, France Adaptation cardiovasculaire à l'ischémie, Bordeaux University, U1034, Pessac, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Moreau
authors.affiliation: Adaptation cardiovasculaire à l'ischémie, INSERM U1034, 125 Avenue du Haut Lévèque, 33 600 Pessac, France Adaptation cardiovasculaire à l'ischémie, Bordeaux University, U1034, Pessac, France Department of Cardiology, Pôle Cardiothoracique, Hôpital Haut Lévêque, Pessac, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Couffinhal
authors.affiliation: Adaptation cardiovasculaire à l'ischémie, INSERM U1034, 125 Avenue du Haut Lévèque, 33 600 Pessac, France Adaptation cardiovasculaire à l'ischémie, Bordeaux University, U1034, Pessac, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Duplàa
authors.affiliation: Adaptation cardiovasculaire à l'ischémie, INSERM U1034, 125 Avenue du Haut Lévèque, 33 600 Pessac, France Adaptation cardiovasculaire à l'ischémie, Bordeaux University, U1034, Pessac, France pascale.dufourcq@u-bordeaux2.fr.
authors.forename: Pascale
authors.initials: P
authors.lastname: Dufourcq
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002199:Capillary Permeability / Q000502:physiology*; D002450:Cell Communication; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D051157:Frizzled Receptors; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495267:CTNNB1 protein, mouse; D015820:Cadherins; D051157:Frizzled Receptors; C492041:Fzd7 protein, mouse; D043562:Receptors, G-Protein-Coupled; D051176:beta Catenin; D038362:Glycogen Synthase Kinase 3
keywords: Cadherin; Endothelial cell; Transgenic mice; Vascular permeability; Wnt/frizzled signalling