CFTR expression decreases with age in several airway cell types

Abstract

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.

Keywords: CFTR; Lung aging; Mucociliary clearance; Mucus.

Fig. 1

CFTR expression by decade. Bulk RNA sequencing data from lung tissue. Data is from the GTEx portal (18).

Fig. 2

CFTR expression by decade. Single cell seq data from lung tissue in the CELLxGENE single-cell human cell atlas for: (A) Goblet cells, (B) Club cells, (C) Ciliated cells, (D) Basal Cells.