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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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https://hal-pasteur.archives-ouvertes.fr/pasteur-02863041
Contributor : Yongzheng Wu <>
Submitted on : Tuesday, June 9, 2020 - 8:30:26 PM
Last modification on : Tuesday, September 1, 2020 - 3:21:49 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, European Respiratory Society, 2013, 42 (6), pp.1553-1562. ⟨10.1183/09031936.00164212⟩. ⟨pasteur-02863041⟩

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