TY - JOUR T1 - CFTR dysfunction induces vascular endothelial growth factor synthesis in airway epithelium JF - European Respiratory Journal JO - Eur Respir J SP - 1553 LP - 1562 DO - 10.1183/09031936.00164212 VL - 42 IS - 6 AU - Clémence Martin AU - Nathalie Coolen AU - Yongzheng Wu AU - Guiti Thévenot AU - Lhousseine Touqui AU - Virginie Prulière-Escabasse AU - Jean-François Papon AU - André Coste AU - Estelle Escudier AU - Daniel J. Dusser AU - Isabelle Fajac AU - Pierre-Régis Burgel Y1 - 2013/12/01 UR - http://erj.ersjournals.com/content/42/6/1553.abstract N2 - 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-inh172 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. CFTR dysfunction triggers epithelial synthesis of VEGF-A, which may contribute to vascular remodelling http://ow.ly/p7ebY ER -