The Nicotinic Receptor Polymorphism rs16969968 Is Associated with Airway Remodeling and Inflammatory Dysregulation in COPD Patients.
Fiche publication
Date publication
septembre 2022
Journal
Cells
Auteurs
Membres identifiés du Cancéropôle Est :
Pr POLETTE Myriam, Dr DORMOY Valerian
Tous les auteurs :
Saber Cherif L, Diabasana Z, Perotin JM, Ancel J, Petit LMG, Devilliers MA, Bonnomet A, Lalun N, Delepine G, Maskos U, Gosset P, Polette M, Muggeo A, Guillard T, Deslée G, Dormoy V
Lien Pubmed
Résumé
Genome-wide association studies unveiled the associations between the single nucleotide polymorphism rs16969968 of CHRNA5, encoding the nicotinic acetylcholine receptor alpha5 subunit (α5SNP), and nicotine addiction, cancer, and COPD independently. Here, we investigated α5SNP-induced epithelial remodeling and inflammatory response in human COPD airways. We included 26 α5SNP COPD patients and 18 wild-type α5 COPD patients in a multi-modal study. A comparative histologic analysis was performed on formalin-fixed paraffin-embedded lung tissues. Isolated airway epithelial cells from bronchial brushings were cultivated in the air-liquid interface. Broncho-alveolar fluids were collected to detect inflammatory mediators. Ciliogenesis was altered in α5SNP COPD bronchial and bronchiolar epithelia. Goblet cell hyperplasia was exacerbated in α5SNP small airways. The broncho-alveolar fluids of α5SNP COPD patients exhibited an increase in inflammatory mediators. The involvement of the rs16969968 polymorphism in airway epithelial remodeling and related inflammatory response in COPD prompts the development of innovative personalized diagnostic and therapeutic strategies.
Mots clés
COPD, airways, epithelial remodeling, inflammation, nicotinic receptors, rs16969968
Référence
Cells. 2022 09 20;11(19):