Down‐expression of Foxj1 on airway epithelium with impaired cilia architecture in non‐cystic fibrosis bronchiectasis implies disease severity

• Published in: The clinical respiratory journal 2023-05, Vol.17 (5), p.405-413
• Main Authors: Zou, Xiao‐Ling, Yang, Hai‐Ling, Ding, Wen‐Wen, Li, Hai‐Ke, Zhou, Yu‐Qi, Zhang, Tian‐Tuo
• Format: Article
• Language: English
• Subjects: airway epithelium; Bronchiectasis - pathology; Cilia; cilia disorder; Cystic fibrosis; Epithelium - metabolism; forkhead box protein j1; Forkhead Transcription Factors - metabolism; Humans; Hyperplasia; Hyperplasia - metabolism; Hyperplasia - pathology; Lung - pathology; non‐cystic fibrosis bronchiectasis; Original; pathogenesis; Patient Acuity
• ISSN: 1752-6981; 1752-699X
• DOI: 10.1111/crj.13605

Introduction The pathogenesis of non‐cystic fibrosis bronchiectasis has not been clearly clarified. This study aimed to investigate the expression of ciliary regulating protein forkhead box protein j1 (Foxj1) on airway epithelium in non‐cystic fibrosis bronchiectasis and its association with airway cilia structure disorder and disease severity. Methods Lung tissue sections excised from 47 patients with non‐cystic fibrosis bronchiectasis were included between January 2018 and June 2021. Specimens from 26 subjects who underwent a lobectomy due to lung nodule were chosen as controls. Clinical information was collected, and pathologic analysis was performed to assess the epithelial structure and expression of ciliary regulating Foxj1. Results Of the 47 patients with non‐cystic fibrosis bronchiectasis, 25 were considered as mild, 12 were moderate whereas the remaining 10 cases were severe according to the bronchiectasis severity index score evaluation. Epithelial hyperplasia, hyperplasia of goblet cells and inflammatory cell infiltration were observed in non‐cystic fibrosis bronchiectasis, compared with control subjects. Cilia length in non‐cystic fibrosis bronchiectasis patients were shorter than that in the control group, (5.34 ± 0.89) μm versus (7.34 ± 0.71) μm, respectively (P = 0.002). The expression of Foxj1 was (2.69 ± 1.09) × 106 in non‐cystic fibrosis bronchiectasis, compared with (6.67 ± 1.15) × 106 in the control group (P = 0.001). Moreover, patients with lower expression of Foxj1 showed shorter airway cilia and worse in disease severity. Conclusion Foxj1 declined in the airway epithelium of patients with non‐cystic fibrosis bronchiectasis, positively correlated to cilia length and might imply worse disease severity. The present study found that expression of forkhead box protein j1 (Foxj1) declined in the airway epithelium of patients with non‐CF BE and was related to cilia length and disease severity. It indicated that downregulation of Foxj1 might play an important role in pathogenesis and development of non‐CF BE by modulating airway cilia function.