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CFTR dysfunction induces vascular endothelial growth factor synthesis in airway epithelium

Abstract : 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.
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Contributor : Yongzheng Wu Connect in order to contact the contributor
Submitted on : Tuesday, June 9, 2020 - 8:30:26 PM
Last modification on : Friday, August 5, 2022 - 10:30:03 AM

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Clémence Martin, Nathalie Coolen, Yongzheng Wu, Guiti Thévenot, Lhousseine Touqui, et al.. CFTR dysfunction induces vascular endothelial growth factor synthesis in airway epithelium. European Respiratory Journal, 2013, 42 (6), pp.1553-1562. ⟨10.1183/09031936.00164212⟩. ⟨pasteur-02863041⟩



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