Li Kuan, Song Zhaoyu, Yue Qing, Wang Qi, Li Yu, Zhu Yu, Chen Huaiyong
Department of Respiratory Medicine, Haihe Hospital, Tianjin University, 300350, Tianjin, China.
Tianjin Key Laboratory of Lung Regenerative Medicine, Haihe Hospital, Tianjin University, 300350, Tianjin, China.
Heliyon. 2024 Jul 4;10(13):e34105. doi: 10.1016/j.heliyon.2024.e34105. eCollection 2024 Jul 15.
Hypersecretion of airway mucus caused by goblet cell metaplasia is a characteristic of chronic pulmonary inflammatory diseases including asthma, cystic fibrosis (CF), and chronic obstructive pulmonary disease (COPD). Goblet cells originate from airway progenitor club cells. However, the molecular mechanisms and features of goblet cell metaplasia in lung disease are poorly understood. Herein, public single-cell RNA sequencing datasets of human lungs were reanalyzed to explore the transitional phase as club cells differentiate into goblet cells in asthma, CF, and COPD. We found that changes in club and goblet cells during pathogenesis and cellular transition were associated with signalling pathways related to immune response, oxidative stress, and apoptosis. Moreover, other key drivers of goblet cell specification appeared to be pathologically specific, with interleukin (IL)-13 and hypoxia inducible factor 1 (HIF-1)-induced genetic changes in asthma, cystic fibrosis transmembrane conductance regulator (CFTR) mutation being present in CF, and interactions with CD8 T cells, mitophagy, and mitochondria-induced apoptosis in COPD. In conclusion, this study revealed the similarities and differences in goblet cell metaplasia in asthma, CF, and COPD at the transcriptome level, thereby providing insights into possible novel therapeutic approaches for these diseases.
杯状细胞化生引起的气道黏液高分泌是包括哮喘、囊性纤维化（CF）和慢性阻塞性肺疾病（COPD）在内的慢性肺部炎症性疾病的一个特征。杯状细胞起源于气道祖细胞——俱乐部细胞。然而，肺部疾病中杯状细胞化生的分子机制和特征尚不清楚。在此，我们重新分析了人类肺部的公开单细胞RNA测序数据集，以探索在哮喘、CF和COPD中俱乐部细胞分化为杯状细胞的过渡阶段。我们发现，发病机制和细胞转变过程中俱乐部细胞和杯状细胞的变化与免疫反应、氧化应激和凋亡相关的信号通路有关。此外，杯状细胞特化的其他关键驱动因素似乎具有病理特异性，在哮喘中有白细胞介素（IL）-13和缺氧诱导因子1（HIF-1）诱导的基因变化，CF中存在囊性纤维化跨膜传导调节因子（CFTR）突变，而在COPD中有与CD8 T细胞的相互作用、线粒体自噬和线粒体诱导的凋亡。总之，本研究揭示了哮喘、CF和COPD在转录组水平上杯状细胞化生的异同，从而为这些疾病可能的新治疗方法提供了见解。
