Immunology & Respiratory Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany.
Department of General Physiology, University of Ulm, Ulm, Germany.
Sci Rep. 2020 Apr 10;10(1):6257. doi: 10.1038/s41598-020-63345-5.
Cigarette smoke (CS) is the leading risk factor to develop COPD. Therefore, the pathologic effects of whole CS on the differentiation of primary small airway epithelial cells (SAEC) were investigated, using cells from three healthy donors and three COPD patients, cultured under ALI (air-liquid interface) conditions. The analysis of the epithelial physiology demonstrated that CS impaired barrier formation and reduced cilia beat activity. Although, COPD-derived ALI cultures preserved some features known from COPD patients, CS-induced effects were similarly pronounced in ALI cultures from patients compared to healthy controls. RNA sequencing analyses revealed the deregulation of marker genes for basal and secretory cells upon CS exposure. The comparison between gene signatures obtained from the in vitro model (CS vs. air) with a published data set from human epithelial brushes (smoker vs. non-smoker) revealed a high degree of similarity between deregulated genes and pathways induced by CS. Taken together, whole cigarette smoke alters the differentiation of small airway basal cells in vitro. The established model showed a good translatability to the situation in vivo. Thus, the model can help to identify and test novel therapeutic approaches to restore the impaired epithelial repair mechanisms in COPD, which is still a high medical need.
香烟烟雾（CS）是导致 COPD 发生的主要危险因素。因此，本研究采用来自 3 名健康供体和 3 名 COPD 患者的原代小气道上皮细胞（SAEC），在 ALI 条件下培养，以研究 CS 对 SAEC 分化的整体影响。上皮生理学分析表明，CS 会损害屏障形成并降低纤毛摆动活性。尽管 COPD 衍生的 ALI 培养物保留了一些来自 COPD 患者的特征，但 CS 诱导的效应在 COPD 患者和健康对照者的 ALI 培养物中同样明显。RNA 测序分析显示 CS 暴露后，标记基底细胞和分泌细胞的基因失调。将体外模型（CS 与空气）中的基因特征与来自人上皮刷的已发表数据集（吸烟者与非吸烟者）进行比较，结果表明 CS 诱导的基因和通路失调与体外模型非常相似。总之，香烟烟雾会改变小气道基底细胞的体外分化。建立的模型显示出很好的体内外转化能力。因此，该模型可用于鉴定和测试新的治疗方法，以恢复 COPD 中受损的上皮修复机制，这仍然是一个巨大的医疗需求。
