Impact of rs16969968 polymorphism (SNPα5) on epithelial differentiation in COPD patients - Université de Reims Champagne-Ardenne Access content directly
Conference Poster Year : 2022

Impact of rs16969968 polymorphism (SNPα5) on epithelial differentiation in COPD patients

Abstract

Background Genome-wide association studies unveiled the association of rs16969968 present on the α5 subunit of nicotinic receptors with nicotine addiction, cancer, and chronic obstructive pulmonary disease independently, but no biological data is available in humans. Aims and Objectives We previously demonstrated that rs16969968 impaired ciliogenesis and cytokine production in respiratory epithelia. Here, we investigated the role of rs16969968 in the context of COPD. We suggest it is involved in bronchial and bronchiolar remodeling and differentiation and therefore participates in COPD pathogenesis. Methods Lung tissues from COPD patients (n=23) were genotyped to identify the rs16969968 polymorphism. Immunostainings on bronchial and bronchiolar sections were performed to analyze histological features. Air-liquid interface cultures from bronchial brushings of COPD patients (n=8) were analyzed after 15 days of differentiation to assess ciliogenesis. Results Bronchiolar SNPα5 COPD sections presented a 23% increase of basal cells (p<0.05), and a 122% increase of Muc5ac secretory cells (p<0.001), without affecting cilia. The bronchial SNPα5 COPD tissues did not differ compared to wild-type α5. However, in vitro analysis, revealed a 33% increase of primary cilia (p<0.01) in differentiated epithelia of SNPα5 COPD patients. Conclusions These results highlighted the participation of SNPα5 in the remodeling of bronchial and bronchiolar epithelium, affecting the basal cells, primary cilia, and the secretion of Muc5ac in COPD patients.
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Dates and versions

hal-04601595 , version 1 (05-06-2024)

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Lynda Saber Cherif, Zania Diabasana, Jeanne‐marie Perotin, Julien Ancel, Uwe Maskos, et al.. Impact of rs16969968 polymorphism (SNPα5) on epithelial differentiation in COPD patients. ERS, Sep 2022, Barcelone (ES), Spain. ⟨10.1183/13993003.congress-2022.1288⟩. ⟨hal-04601595⟩
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