{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:37:26Z","timestamp":1788543446120,"version":"build-2803163510"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000362","name":"Asthma and Lung UK","doi-asserted-by":"publisher","award":["AUK\u2010PG\u20102013\u2010208"],"award-info":[{"award-number":["AUK\u2010PG\u20102013\u2010208"]}],"id":[{"id":"10.13039\/501100000362","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004328","name":"Genentech","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004328","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013342","name":"NIHR Imperial Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013342","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020013","name":"NIHR Leicester Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Airway remodelling is a feature of severe asthma with airway epithelial damage observed frequently. We evaluated the role of WNT5a and TGF\u2010\u03b2\n                      <jats:sub>1<\/jats:sub>\n                      in asthmatic airway biopsies and in sputum and bronchial brushings assessed their role in remodelling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      WNT5a and TGF\u2010\u03b2\n                      <jats:sub>1<\/jats:sub>\n                      protein expression were assessed in the lamina propria epithelium of people with asthma (GINA 1\u20133, n\u20108 and GINA 4\u20135, n\u201014) and healthy subjects (n\u20109), alongside relevant remodelling markers. The effects of WNT5a and TGF\u2010\u03b2\n                      <jats:sub>1<\/jats:sub>\n                      on BEAS\u20102B epithelial cell wound healing and differentiation were assessed in\u00a0vitro. Replication was performed in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U\u2010BIOPRED) study in sputum (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009120) and bronchial brushes (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009147).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      WNT5a and TGF\u2010\u03b2\n                      <jats:sub>1<\/jats:sub>\n                      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\u2010localised predominantly to airway basal cells and correlated with Th17 gene expression (\n                      <jats:italic>r<\/jats:italic>\n                      \u2009=\u20090.40,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.025) and both the % intact (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>s<\/jats:sub>\n                      \u2009=\u20090.54,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001) and % denuded epithelium (\n                      <jats:italic>r<\/jats:italic>\n                      <jats:sub>s<\/jats:sub>\n                      \u2009=\u2009\u22120.39,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003). Experiments in BEAS\u20102B cells confirmed that WNT5a at maximal physiological concentrations (1\u2009\u03bcg\/mL), promoted epithelial wound healing, independently of TGF\u2010\u03b2\n                      <jats:sub>1<\/jats:sub>\n                      , as well as induction of EMT\u2010like morphology. WNT5a mRNA was associated with severe asthma, airflow limitation, sputum eosinophilia and Th2, and Th17 and neutrophil activation transcriptomes in sputum in U\u2010BIOPRED.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>WNT5a is associated with both airway remodelling and severe asthma.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      identifier: NCT01982162\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.16445","type":"journal-article","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T05:15:22Z","timestamp":1735881322000},"page":"1025-1037","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The Role of\n                    <scp>WNT5a<\/scp>\n                    and\n                    <scp>TGF<\/scp>\n                    \u2010\u03b21 in Airway Remodelling and Severe Asthma"],"prefix":"10.1111","volume":"80","author":[{"given":"Tariq","family":"Daud","sequence":"first","affiliation":[{"name":"Department of Respiratory Sciences, College of Life Sciences, and NIHR Biomedical Research Centre (Respiratory Theme) Glenfield Hospital  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheree","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, College of Life Sciences, and NIHR Biomedical Research Centre (Respiratory Theme) Glenfield Hospital  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazanin","family":"Zounemat Kermani","sequence":"additional","affiliation":[{"name":"Data Science Institute Imperial College  London UK"},{"name":"Imperial NIHR Biomedical Research Centre, National Heart and Lung Institute (NHLI) Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Richardson","sequence":"additional","affiliation":[{"name":"Department of Respiratory Sciences, College of Life Sciences, and NIHR Biomedical Research Centre (Respiratory Theme) Glenfield Hospital  Leicester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9176-5564","authenticated-orcid":false,"given":"Liam G.","family":"Heaney","sequence":"additional","affiliation":[{"name":"Wellcome\u2010Wolfson Centre for Experimental Medicine, School of Medicine, Dentistry and 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