%0 Journal Article %T CFTR dysfunction induces vascular endothelial growth factor synthesis in airway epithelium %+ Service de pneumologie [CHU Cochin] %+ Université Paris Descartes - Paris 5 (UPD5) %+ Défense innée et inflammation %+ Service d'ORL [Créteil] %+ Institut Mondor de Recherche Biomédicale (IMRB) %+ CHU Trousseau [APHP] %+ Physiopathologie des maladies génétiques d'expression pédiatrique %+ Service de Physiologie et Explorations Fonctionnelles [Cochin APHP] %A Martin, Clémence %A Coolen, Nathalie %A Wu, Yongzheng %A Thévenot, Guiti %A Touqui, Lhousseine %A Prulière-Escabasse, Virginie %A Papon, Jean-François %A Coste, André %A Escudier, Estelle %A Dusser, Daniel %A Fajac, Isabelle %A Burgel, Pierre-Régis %Z This work was funded by grants from Chancellerie des Universités de Paris (Legs Poix), Association Vaincre la Mucoviscidose and Association Cardif. %< avec comité de lecture %@ 0903-1936 %J European Respiratory Journal %I European Respiratory Society %V 42 %N 6 %P 1553-1562 %8 2013-11-30 %D 2013 %R 10.1183/09031936.00164212 %M 23520314 %Z Life Sciences [q-bio]/Human health and pathology/Infectious diseases %Z Life Sciences [q-bio]/Microbiology and Parasitology/BacteriologyJournal articles %X Peribronchial angiogenesis may occur in cystic fibrosis and vascular endothelial growth factor (VEGF)-A regulates angiogenesis in airways. Peribronchial vascularity and VEGF-A expression were examined using immunocytochemistry and morphometric analysis in lung sections obtained in 10 cystic fibrosis patients at transplantation versus 10 control nonsmokers, and in two strains of Cftr-deficient mice versus wild-type littermates. Airway epithelial NCI-H292 cells and primary cultures of noncystic fibrosis human airway epithelial cells were treated with cystic fibrosis transmembrane conductance regulator (CFTR) inhibitors (CFTR-inh(172) or PPQ-102) or transfected with a CFTR small interfering (si)RNA with or without a selective epidermal growth factor receptor tyrosine kinase inhibitor. Concentrations of VEGF-A and phosphorylated epidermal growth factor receptor were measured by ELISA. Peribronchial vascularity was increased in cystic fibrosis patients, but not in Cftr-deficient mice. VEGF-A immunostaining was localised to airway epithelium and was increased in cystic fibrosis patients and in Cftr-deficient mice. In cultured airway epithelial cells, treatment with CFTR inhibitors or transfection with CFTR siRNA induced a twofold increase in VEGF-A production. CFTR inhibitors triggered epidermal growth factor receptor phosphorylation that was required for VEGF-A synthesis. Cystic fibrosis airways at transplantation showed increased peribronchial vascularity and epithelial VEGF-A expression. CFTR dysfunction triggered epithelial synthesis of VEGF-A, which may contribute to vascular remodelling. %G English %Z The authors thank Sophie Danel-Beaucaire (Cochin Hospital, Paris, France) for help with immunohistochemical staining and Claire Danel (Bichat Hospital, Paris, France) for providing human CF tissues. %L pasteur-02863041 %U https://pasteur.hal.science/pasteur-02863041 %~ INSERM %~ PASTEUR %~ UNIV-PARIS5 %~ UPMC %~ APHP %~ IMRB %~ UPEC %~ U933 %~ UPMC_POLE_4 %~ SORBONNE-UNIVERSITE %~ SU-INF-2018 %~ SU-MEDECINE %~ SU-MED %~ UNIV-PARIS %~ SU-TI %~ ALLIANCE-SU