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Frizzled7 controls vascular permeability through the Wnt-canonical pathway and cross-talk with endothelial cell junction complexes.
Ferreira Tojais, Nancy; Peghaire, Claire; Franzl, Nathalie; Larrieu-Lahargue, Frédéric; Jaspard, Béatrice; Reynaud, Annabelle; Moreau, Catherine; Couffinhal, Thierry; Duplàa, Cécile; Dufourcq, Pascale.
Afiliación
  • Ferreira Tojais N; 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.
  • Peghaire C; 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.
  • Franzl N; 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.
  • Larrieu-Lahargue F; 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.
  • Jaspard B; 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.
  • Reynaud A; 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.
  • Moreau C; 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.
  • Couffinhal T; 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.
  • Duplàa C; 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.
  • Dufourcq P; 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.
Cardiovasc Res ; 103(2): 291-303, 2014 Jul 15.
Article en En | MEDLINE | ID: mdl-24866384
AIMS: 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. METHODS AND RESULTS: Fzd7 is expressed in endothelial cells and accumulates at the points of cell-cell contact in association with VE-cadherin and ß-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 ß-catenin expression, a decrease in their association and an increase of tyrosine phosphorylation of VE-cadherin/ß-catenin. Fzd7 transduces a Wnt/ß-catenin signalling cascade that is required to regulate ß-catenin and canonical target gene expression. Finally, LiCl, a GSK3 inhibitor, and ß-catenin overexpression rescued endothelial integrity and adherens junction organization, induced by fzd7 deletion. CONCLUSION: 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Permeabilidad Capilar / Cadherinas / Células Endoteliales / Receptores Acoplados a Proteínas G / Vía de Señalización Wnt Límite: Animals Idioma: En Revista: Cardiovasc Res Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Permeabilidad Capilar / Cadherinas / Células Endoteliales / Receptores Acoplados a Proteínas G / Vía de Señalización Wnt Límite: Animals Idioma: En Revista: Cardiovasc Res Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido