The role of WNT5a and TGF-β1 in airway remodelling and severe asthma
File(s)
Accepted version
Accepted version
Author(s)
Type
Journal Article
Abstract
Background
Airway remodelling is a feature of severe asthma with airway epithelial damage observed frequently. We evaluated the role of WNT5a and TGF-β1 in asthmatic airway biopsies and in sputum and bronchial brushings assessed their role in remodelling.
Methods
WNT5a and TGF-β1 protein expression were assessed in the lamina propria epithelium of people with asthma (GINA 1–3, n-8 and GINA 4–5, n-14) and healthy subjects (n-9), alongside relevant remodelling markers. The effects of WNT5a and TGF-β1 on BEAS-2B epithelial cell wound healing and differentiation were assessed in vitro. Replication was performed in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) study in sputum (n = 120) and bronchial brushes (n = 147).
Results
WNT5a and TGF-β1 protein expression were significantly increased in the airway epithelium and lamina propria in asthma patients with concurrent airflow limitation or severe disease. Furthermore, WNT5a protein expression in the lamina propria correlated with tissue eosinophils and vascular remodelling. Airway epithelial WNT5a was co-localised predominantly to airway basal cells and correlated with Th17 gene expression (r = 0.40, p = 0.025) and both the % intact (rs = 0.54, p = 0.001) and % denuded epithelium (rs = −0.39, p = 0.003). Experiments in BEAS-2B cells confirmed that WNT5a at maximal physiological concentrations (1 μg/mL), promoted epithelial wound healing, independently of TGF-β1, as well as induction of EMT-like morphology. WNT5a mRNA was associated with severe asthma, airflow limitation, sputum eosinophilia and Th2, and Th17 and neutrophil activation transcriptomes in sputum in U-BIOPRED.
Conclusion
WNT5a is associated with both airway remodelling and severe asthma.
Airway remodelling is a feature of severe asthma with airway epithelial damage observed frequently. We evaluated the role of WNT5a and TGF-β1 in asthmatic airway biopsies and in sputum and bronchial brushings assessed their role in remodelling.
Methods
WNT5a and TGF-β1 protein expression were assessed in the lamina propria epithelium of people with asthma (GINA 1–3, n-8 and GINA 4–5, n-14) and healthy subjects (n-9), alongside relevant remodelling markers. The effects of WNT5a and TGF-β1 on BEAS-2B epithelial cell wound healing and differentiation were assessed in vitro. Replication was performed in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) study in sputum (n = 120) and bronchial brushes (n = 147).
Results
WNT5a and TGF-β1 protein expression were significantly increased in the airway epithelium and lamina propria in asthma patients with concurrent airflow limitation or severe disease. Furthermore, WNT5a protein expression in the lamina propria correlated with tissue eosinophils and vascular remodelling. Airway epithelial WNT5a was co-localised predominantly to airway basal cells and correlated with Th17 gene expression (r = 0.40, p = 0.025) and both the % intact (rs = 0.54, p = 0.001) and % denuded epithelium (rs = −0.39, p = 0.003). Experiments in BEAS-2B cells confirmed that WNT5a at maximal physiological concentrations (1 μg/mL), promoted epithelial wound healing, independently of TGF-β1, as well as induction of EMT-like morphology. WNT5a mRNA was associated with severe asthma, airflow limitation, sputum eosinophilia and Th2, and Th17 and neutrophil activation transcriptomes in sputum in U-BIOPRED.
Conclusion
WNT5a is associated with both airway remodelling and severe asthma.
Date Issued
2025-04-01
Date Acceptance
2024-11-07
Citation
Allergy, 2025, 80 (4), pp.1025-1037
ISSN
0105-4538
Publisher
Wiley
Start Page
1025
End Page
1037
Journal / Book Title
Allergy
Volume
80
Issue
4
Copyright Statement
Copyright © 2025 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39749571
Subjects
TGF‐β1
WNT5a
airway remodelling
asthma
Publication Status
Published
Coverage Spatial
Denmark
Date Publish Online
2025-01-03