Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease attributed to the complex interplay of genetic and environmental risks. The muco-ciliary clearance (MCC) system plays a critical role in maintaining the conduit for air to and from the alveoli, but it remains poorly understood whether the MCC abnormalities in conducting airway are involved in IPF pathogenesis. In this study, we obtained the surgically resected bronchi and peripheral lung tissues from 31 IPF patients and 39 control subjects, and we sought to explore the morphologic characteristics of MCC in conducting airway by using immunostaining and scanning and transmission electron microscopy. In the submucosal regions of the bronchi, we found that the areas of mucus glands (MUC5B+) were significantly larger in IPF patients as compared with control subjects (p < 0.05). In the surface epithelium of three airway regions (bronchi, proximal bronchioles, and distal bronchioles), increased MUC5B and MUC5AC expression of secretory cells, decreased number of ciliated cells, and increased ciliary length were observed in IPF patients than control subjects (all p < 0.05). In addition, the mRNA expression levels of MUC5B were up-regulated in both the bronchi and peripheral lung of IPF patients than those of control subjects (p < 0.05), accompanied with 93.55% IPF subjects who had obvious MUC5B+ mucus plugs in alveolar regions. No MUC5B rs35705950 single-nucleotide polymorphism allele was detected in both IPF patients and control subjects. Our study shows that mucus hypersecretion and ciliary impairment in conducting airway are major causes of mucus plugs in alveolar regions and may be closely related to the alveolar injuries in IPF patients.
Highlights
BackgroundIdiopathic pulmonary fibrosis (IPF) is the most common type of idiopathic interstitial pneumonia characterized by gas exchange impairment, progressive dyspnea, and overall poor prognosis, for which there is restricted treatment options (Mora et al, 2017; Khanna et al, 2020)
The highest genetic risk factor for sporadic IPF is a common variant in single-nucleotide polymorphism (SNP) for Mucin 5B (MUC5B) promoter region, which has been confirmed in several independent cohorts, predominantly in Caucasians (Allen et al, 2017; Hobbs et al, 2019)
The allele frequency for the polymorphism MUC5B rs35705950 was not detected in both control subjects (0/20) and IPF patients (0/20) of our Chinese cohort
Summary
BackgroundIdiopathic pulmonary fibrosis (IPF) is the most common type of idiopathic interstitial pneumonia characterized by gas exchange impairment, progressive dyspnea, and overall poor prognosis, for which there is restricted treatment options (Mora et al, 2017; Khanna et al, 2020). The highest genetic risk factor for sporadic IPF is a common variant in single-nucleotide polymorphism (SNP) for MUC5B promoter region (rs35705950), which has been confirmed in several independent cohorts, predominantly in Caucasians (Allen et al, 2017; Hobbs et al, 2019). It remains elusive whether the MCC abnormalities in conducting airways are common pathologic characteristics in Chinese IPF patients, and further studies to quantify the distribution of secretory cells as well as characterize the morphological features of ciliated cells in conducting airway of these patients are warranted
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