{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:43:30Z","timestamp":1792212210377,"version":"4.4.0"},"reference-count":39,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI24\/00169"],"award-info":[{"award-number":["PI24\/00169"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CD23\/00192"],"award-info":[{"award-number":["CD23\/00192"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014849","name":"Conselleria de Cultura, Educaci\u00f3n y Ciencia, Generalitat Valenciana","doi-asserted-by":"publisher","award":["CIAPOS\/2024\/317"],"award-info":[{"award-number":["CIAPOS\/2024\/317"]}],"id":[{"id":"10.13039\/501100014849","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disease in which persistent remodeling and fibrosis may contribute to corticosteroid refractoriness. Membrane\u2010tethered mucins, particularly MUC16, may regulate profibrotic and steroid\u2010response pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine whether MUC16 is associated with fibrosis and corticosteroid insensitivity in CRSwNP and to define its functional effects in fibroblasts and epithelial cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Nasal polyp tissue from CRSwNP subgroups, including oral corticosteroid\u2010resistant patients, was analyzed by histology, immunohistochemistry, hydroxyproline quantification, and RT\u2010qPCR. Primary nasal polyp fibroblasts and epithelial cells, and MRC5, BEAS2B, and HeLa cells, were stimulated with TGF\u2010\u03b21 or LPS and treated with dexamethasone. MUC16 was silenced with siRNA, and profibrotic and glucocorticoid\u2010response pathways were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Oral corticosteroid\u2010resistant polyps showed the highest fibrosis (collagen, \u03b1\u2010SMA\u2010positive fibroblasts, TGF\u2010\u03b21, hydroxyproline), despite not being the most eosinophilic. MUC16 increased in these polyps and correlated with hydroxyproline. Their fibroblasts, overexpressing MUC16, showed reduced dexamethasone inhibition of TGF\u2010\u03b21\u2010induced collagen I and proliferation. MUC16 silencing reduced phospho\u2010SMAD3 and Smad\u2010binding element activity, restored dexamethasone sensitivity, and reduced proliferation. In epithelium, MUC16 silencing enhanced dexamethasone suppression of LPS\u2010induced IL\u20106, reduced STAT3 phosphorylation, and increased glucocorticoid response element activity, GR Ser211 phosphorylation, and MKP1 induction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In human polyp tissue, MUC16 is associated with a fibrotic, corticosteroid\u2010insensitive CRSwNP phenotype, whereas its causal link with impaired glucocorticoid signaling is supported by in\u00a0vitro loss\u2010of\u2010function experiments. MUC16 may represent a candidate biomarker and potential therapeutic target in refractory CRSwNP, although prospective validation as an endotype\u2010defining biomarker is still required.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/all.70541","type":"journal-article","created":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:31:27Z","timestamp":1792211487000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>MUC16<\/scp>\n                    Defines a Fibrotic Endotype With Corticosteroid Insensitivity in Nasal Polyps"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5929-5486","authenticated-orcid":false,"given":"Paula","family":"Montero","sequence":"first","affiliation":[{"name":"Research Foundation of the University General Hospital of Valencia  Valencia Spain"},{"name":"CIBER de enfermedades respiratorias, Health Institute Carlos III  Valencia Spain"},{"name":"Department of Pharmacology, Faculty of Medicine University of Valencia  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7741-6600","authenticated-orcid":false,"given":"Ines","family":"Roger","sequence":"additional","affiliation":[{"name":"Research Foundation of the University General Hospital of Valencia  Valencia Spain"},{"name":"CIBER de enfermedades respiratorias, Health Institute Carlos III  Valencia Spain"},{"name":"Department of Pharmacology, Faculty of Medicine University of Valencia  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7002-7792","authenticated-orcid":false,"given":"Anselm","family":"Morell","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine University of Valencia  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rub\u00e9n","family":"Serrano\u2010Santos","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine University of Valencia  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4187-1631","authenticated-orcid":false,"given":"Oscar","family":"Villarroya\u2010Palomo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine University of Valencia  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8258-6292","authenticated-orcid":false,"given":"Miguel","family":"Armengot","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Valencia  Valencia Spain"},{"name":"Otorhinolaryngology Unit Hospital Polit\u00e9cnico y Universitario La Fe  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Cortijo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine University of Valencia  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6033-4211","authenticated-orcid":false,"given":"Javier","family":"Milara","sequence":"additional","affiliation":[{"name":"Research Foundation of the University General Hospital of Valencia  Valencia Spain"},{"name":"CIBER de enfermedades respiratorias, Health Institute Carlos III  Valencia Spain"},{"name":"Department of Pharmacology, Faculty of Medicine University of Valencia  Valencia Spain"},{"name":"Pharmacy Unit University General Hospital Consortium of Valencia  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"issue":"3","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.jaci.2018.12.986","article-title":"Prevalence of Chronic Rhinosinusitis in the General Population Based on Sinus Radiology and Symptomatology","volume":"143","author":"Dietz de Loos D.","year":"2019","journal-title":"Journal of Allergy and Clinical Immunology"},{"issue":"29","key":"e_1_2_11_3_1","first-page":"1","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2020","volume":"58","author":"Fokkens W. 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