Inserm P3Cell UMR-S 1250, Université de Reims Champagne-Ardenne, 51092 Reims, France.
Département des Maladies Respiratoires, CHU de Reims, 51092 Reims, France.
Cells. 2022 Sep 20;11(19):2937. doi: 10.3390/cells11192937.
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.
全基因组关联研究揭示了单核苷酸多态性 rs16969968 与尼古丁成瘾、癌症和 COPD 的独立关联，该 SNP 位于编码烟碱型乙酰胆碱受体α5 亚基（α5SNP）的 CHRNA5 基因上。在这里，我们研究了 α5SNP 诱导的人类 COPD 气道上皮重塑和炎症反应。我们纳入了 26 例 α5SNP COPD 患者和 18 例野生型 α5 COPD 患者进行多模式研究。对福尔马林固定石蜡包埋的肺组织进行了对比组织学分析。从支气管刷取物中分离出气道上皮细胞，在气液界面培养。收集支气管肺泡液以检测炎症介质。α5SNP COPD 支气管和细支气管上皮的纤毛生成发生改变。α5SNP 小气道中的杯状细胞增生加剧。α5SNP COPD 患者的支气管肺泡液中炎症介质增加。rs16969968 多态性在 COPD 气道上皮重塑和相关炎症反应中的参与促使创新性的个性化诊断和治疗策略的发展。
