Protein Profiles in Fibrotic Honeycomb Airway Cells
Spatial proteomics has allowed researchers to create an unbiased protein map of lung cells affected by fibrosis/UIP. They found that the honeycombed cells of the airways are the main site of mucin production and cilia loss. The study also showed that the uninvolved fibrotic airway cells have an abnormal protein signature. This suggests that targeting these cells could slow the progression of fibrosis.
Usual Interstitial Pneumonia (UIP) is a fibrotic disease associated with various fibrotic conditions. UIP is characterized by patchy lung tissue with normal-looking regions adjacent to dense fibrosis and honeycombing, which refers to clustering of airspaces within fibrotic tissue. Mucus and airway debris accumulation in honeycomb airways can impair lung function. Our understanding of fibrotic airway pathogenesis has improved through structural, genetic, and molecular analyses. Reduced numbers of terminal bronchioles and genetic changes affecting alveolar cells have been reported in UIP/IPF lungs. Honeycomb airways comprise various cell types and exhibit marked cellular heterogeneity. The mucus hydrogel that fills and plugs honeycomb airways is underpinned by two gel-forming mucins, with MUC5B being the most abundant. A gain-of-function MUC5B polymorphism is a significant risk factor for lung fibrosis. However, the molecular composition of the mucus plug in UIP is not fully understood.
New study: Targeting uninvolved fibrotic airway cells could slow progression of fibrosis
A recently published study aimed to identify the composition of honeycomb airway cells in pulmonary fibrosis, particularly in usual interstitial pneumonia (UIP). Therefore, the researchers used laser capture microdissection coupled with mass spectrometry (LCM-MS) to provide mechanistic themes. The approach is similar to that used to generate a tissue atlas of the fibrotic front of UIP/IPF.
The study shows that fibrotic honeycomb and fibrotic uninvolved airway cells have an abnormal protein profile similar to mucin-rich honeycomb airway cells, suggesting that fibrotic uninvolved airway cells have an abnormal protein profile in the morphologically intact lung. In addition, the researchers explain that honeycomb airway cells are enriched in proteins involved in mucin biogenesis and have fewer cilia-associated proteins. Indeed, the study findings are significant for identifying key targets and pathways to interrupt fibrosis progression. The study also identifies the composition of mucus in the honeycombed airways in pulmonary fibrosis and compares it to lung cancer (mucinous adenocarcinoma) to determine whether mucus heterogeneity exists in another progressive disease state in which mucus plugs are found in the airways.
Summing up: Impact on the progression and treatment of pulmonary fibrosis
In summary, spatial proteomics has allowed researchers to create an unbiased protein map of lung cells affected by fibrosis/UIP. They found that the honeycombed cells of the airways are the main site of mucin production and cilia loss. The study also showed that the uninvolved fibrotic airway cells have an abnormal protein signature. This suggests that targeting these cells could slow the progression of fibrosis.