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Implication du polymorphisme rs16969968 de la sous-unité alpha5 des récepteurs nicotiniques dans l'homéostasie pulmonaire et la bronchopneumopathie chronique obstructive

Abstract : Genome-Wide Association Studies (GWAS) associated CHRNA5 polymorphism rs16969968 (SNPα5) coding α5nAChR subunit with smoking behavior, decreased respiratory function, and Chronic Obstructive Pulmonary Disease (COPD) onset. We proposed to establish the relationship between SNPα5 and lung biological events characteristic of COPD. Furthermore, nAChRs have been detected in human airways to fill the knowledge gap with a complete lung cartography. We studied their transcriptomic and proteomic profiles in the lung. We demonstrated a differential transcriptomic expression of all subunits depending on the lung compartment and the smoking status, in addition to confirming protein expression of the majority of nAChR subunits in the bronchial epithelium. In vitro and ex vivo, rs16969968 altered ciliogenesis in a non-pathological context and deregulated inflammatory response in early epithelial cell differentiation. Genotyping studies revealed that rs16969968 is more found in COPD patients and correlated with respiratory function impairment and lung emphysema independently of the pathology. Nonetheless, the polymorphism did not influence the bronchial epithelial morphohistology in COPD patients. This pioneering study provided a complete atlas of nAChRs in human airways and cellular and molecular clues to decipher polymorphism rs16969968-associated impairments in the respiratory epithelium of the human lung.
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https://hal.univ-reims.fr/tel-03367469
Contributor : Valerian Dormoy Connect in order to contact the contributor
Submitted on : Wednesday, October 6, 2021 - 11:11:30 AM
Last modification on : Thursday, October 14, 2021 - 1:10:15 PM

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Zania Diabasana. Implication du polymorphisme rs16969968 de la sous-unité alpha5 des récepteurs nicotiniques dans l'homéostasie pulmonaire et la bronchopneumopathie chronique obstructive. Génomique, Transcriptomique et Protéomique [q-bio.GN]. Université Reims Champagne Ardenne, 2021. Français. ⟨tel-03367469⟩

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