CFTR dysfunction induces vascular endothelial growth factor synthesis in airway epithelium
| العنوان: | CFTR dysfunction induces vascular endothelial growth factor synthesis in airway epithelium |
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| المؤلفون: | Nathalie Coolen, Virginie Prulière-Escabasse, Pierre-Régis Burgel, Daniel Dusser, Estelle Escudier, André Coste, Yongzheng Wu, Isabelle Fajac, Lhousseine Touqui, Guiti Thévenot, Clémence Martin, Jean-François Papon |
| المساهمون: | Service de pneumologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Défense innée et inflammation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Service d'ORL [Créteil], Centre Hospitalier Intercommunal de Créteil (CHIC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiopathologie des maladies génétiques d'expression pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Physiologie et Explorations Fonctionnelles [Cochin APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was funded by grants from Chancellerie des Universités de Paris (Legs Poix), Association Vaincre la Mucoviscidose and Association Cardif., 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., Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Wu, Yongzheng |
| المصدر: | European Respiratory Journal European Respiratory Journal, European Respiratory Society, 2013, 42 (6), pp.1553-1562. ⟨10.1183/09031936.00164212⟩ European Respiratory Journal, 2013, 42 (6), pp.1553-1562. ⟨10.1183/09031936.00164212⟩ |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Vascular Endothelial Growth Factor A, Pathology, Cystic Fibrosis, Angiogenesis, medicine.medical_treatment, Cystic Fibrosis Transmembrane Conductance Regulator, MESH: Trachea / metabolism, Cystic fibrosis, Tyrosine-kinase inhibitor, Epithelium, chemistry.chemical_compound, Mice, 0302 clinical medicine, MESH: Cystic Fibrosis Transmembrane Conductance Regulator / physiology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Lung / blood supply, MESH: Animals, MESH: Cystic Fibrosis / physiopathology, Epidermal growth factor receptor, MESH: Cystic Fibrosis / genetics, Phosphorylation, RNA, Small Interfering, Lung, Aorta, Cells, Cultured, 0303 health sciences, biology, MESH: Gene Expression Regulation, MESH: Bronchi / metabolism, respiratory system, 3. Good health, Vascular endothelial growth factor, ErbB Receptors, Trachea, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Mice, Inbred CFTR, MESH: Cells, Cultured, Pulmonary and Respiratory Medicine, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, MESH: Mice, Transgenic, medicine.drug_class, MESH: Aorta / pathology, MESH: ErbB Receptors / metabolism, Bronchi, Mice, Transgenic, Cell Line, 03 medical and health sciences, medicine, Animals, Humans, Mice, Inbred CFTR, MESH: Mice, 030304 developmental biology, MESH: RNA, Small Interfering / metabolism, MESH: Humans, MESH: Phosphorylation, business.industry, Growth factor, MESH: Vascular Endothelial Growth Factor A / metabolism, medicine.disease, MESH: Cystic Fibrosis Transmembrane Conductance Regulator / genetics, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Epithelium / metabolism, MESH: Cell Line, respiratory tract diseases, Transplantation, 030228 respiratory system, chemistry, Gene Expression Regulation, Cancer research, biology.protein, Respiratory epithelium, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business |
| الوصف: | International audience; 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. |
| تدمد: | 1399-3003 0903-1936 |
| DOI: | 10.1183/09031936.00164212⟩ |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::43d50404e016d01b07c398643e380311 https://pubmed.ncbi.nlm.nih.gov/24293414 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....43d50404e016d01b07c398643e380311 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13993003 09031936 |
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| DOI: | 10.1183/09031936.00164212⟩ |