Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, University of Pittsburgh, UPMC MUH NW628, 3459 Fifth Ave, Pittsburgh, PA, 15213, USA.
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.
Sci Rep. 2024 Nov 21;14(1):28832. doi: 10.1038/s41598-024-80108-8.
The mucociliary clearance (MC) system is a vital host defense against infection in the lung. MC system function is dependent on ciliary density, structure, and function and airway surface liquid (ASL) composition and hydration. Animal and human studies indicate that MC rate decreases with age which may contribute to the increased rates of pulmonary infection experienced by older people. The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene encodes an anion channel on epithelial surfaces that plays a key role in maintaining ASL hydration. Failure or dysfunction of CFTR could result in the dehydration of airway mucus, depressing MC. Here we use two available databases including bulk (GTEx) and single-cell (CELLxGENE) sequencing data from the lung to determine if CFTR expression decreases with age. Bulk expression data and single-cell expression data from goblet, club, and respiratory basal cells all demonstrated patterns of decreasing CFTR expression with age. Ciliated airway cells did not. Secretory cells (including club and goblet cells) and basal cells are the largest source of CFTR expression in the airway. This indicates that changes in CFTR expression and ASL dehydration may contribute to the decreasing MC associated with aging.
黏液纤毛清除（MC）系统是肺部抗感染的重要宿主防御机制。MC 系统的功能依赖于纤毛密度、结构和功能以及气道表面液体（ASL）的组成和水合作用。动物和人体研究表明，MC 率随年龄增长而降低，这可能导致老年人肺部感染率增加。囊性纤维化跨膜电导调节因子（CFTR）基因编码上皮表面的阴离子通道，在维持 ASL 水合作用方面发挥着关键作用。CFTR 的失活或功能障碍可能导致气道黏液脱水，从而抑制 MC。在这里，我们使用两个可用的数据库，包括来自肺部的批量（GTEx）和单细胞（CELLxGENE）测序数据，以确定 CFTR 表达是否随年龄而降低。批量表达数据和杯状细胞、俱乐部细胞和呼吸性基底细胞的单细胞表达数据均显示 CFTR 表达随年龄降低的模式。纤毛气道细胞没有。分泌细胞（包括俱乐部细胞和杯状细胞）和基底细胞是气道 CFTR 表达的最大来源。这表明 CFTR 表达和 ASL 脱水的变化可能导致与衰老相关的 MC 降低。
