{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T10:22:50Z","timestamp":1789899770906,"version":"4.0.1"},"reference-count":42,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2015,4,25]],"date-time":"2015-04-25T00:00:00Z","timestamp":1429920000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005640","name":"Flight Attendant Medical Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005640","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int Forum Allergy Rhinol"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The mechanism of airway remodeling in chronic rhinosinusitis with nasal polyposis (CRSwNP) remains unknown. We wished to determine whether profibrotic transforming growth factor beta 1 (TGF\u2010\u03b21) and activin A and their downstream signaling proteins are increased in CRSwNP and if they are regulated in epithelial cells by noxious or inflammatory stimuli.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Frozen tissue from CRSwNP patients, healthy control (HC) middle turbinates, and sinus tissue from CRS without NP (CRSsNP) patients were immunostained for TGF\u2010\u03b21, activin A, and downstream signaling proteins. Primary nasal epithelial cells (PNECs) from HCs and CRSwNP patients were cultured in media, cigarette smoke extract (CSE), or double\u2010stranded RNA (dsRNA) (a ligand for Toll\u2010like receptor\u20103) and examined for inflammatory and profibrotic genes using real\u2010time polymerase chain reaction (PCR).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>CRSwNP patients showed increased TGF\u2010\u03b21 and activin A in the stroma, increased TGF\u2010\u03b21 signaling (phosphorylated Smad2\/3) in the stroma and epithelium, and increased Smad3\u2010dependent Snail1 in the stroma. Immunostaining for TGF\u2010\u03b21, pSmad2\/3, and Snail1 in CRSwNP patients was highly correlated. Immunostaining for pSmad2\/3 and Snail1 was similar in CRSwNP and CRSsNP patients. Compared to HCs, PNECs from CRSwNP patients were more responsive to CSE and dsRNA in terms of TGF\u2010\u03b21 and activin A and more strongly induced by dsRNA in terms of chemokines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Increased TGF\u2010\u03b21 and activin A and increased downstream TGF\u2010\u03b21 signaling is present in CRSwNP patients, primarily in the stroma. This may contribute to features of airway remodeling previously described. PNECs from CRSwNP patients are induced to produce TGF\u2010\u03b21 and activin A by CSE and dsRNA, suggesting that cigarette smoke and viral infection might also contribute to airway remodeling.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.21516","type":"journal-article","created":{"date-parts":[[2015,4,25]],"date-time":"2015-04-25T05:34:55Z","timestamp":1429940095000},"page":"573-582","source":"Crossref","is-referenced-by-count":16,"title":["Profibrotic transforming growth factor beta 1 and activin A are increased in nasal polyp tissue and induced in nasal polyp epithelium by cigarette smoke and Toll\u2010like receptor 3 ligation"],"prefix":"10.1002","volume":"5","author":[{"given":"Moshe","family":"Yamin","sequence":"first","affiliation":[{"name":"Division of Rheumatology Allergy &amp; Immunology, Massachusetts General Hospital  Boston MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric 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