{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T23:51:35Z","timestamp":1784245895860,"version":"3.55.0"},"reference-count":58,"publisher":"BMJ","issue":"11","funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI15C1524"],"award-info":[{"award-number":["HI15C1524"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI17C1669"],"award-info":[{"award-number":["HI17C1669"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2016R1A2B4010407"],"award-info":[{"award-number":["NRF-2016R1A2B4010407"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020R1A2C1012105"],"award-info":[{"award-number":["NRF-2020R1A2C1012105"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020R1A6A1A03043283"],"award-info":[{"award-number":["NRF-2020R1A6A1A03043283"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Thorax"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Epithelial to mesenchymal transition (EMT) is associated with the pathophysiology of chronic rhinosinusitis with nasal polyp (CRSwNP). Wnt signaling is causative for EMT, whereas the mechanism in CRSwNP is not fully understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We sought to evaluate the role of Wnt signaling in EMT of CRSwNP using a murine nasal polyp (NP) model and human tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Inflammatory markers and EMT-related molecules were evaluated in NP models using adenomatosis polyposis coli (Apc)<jats:sup>Min\/+<\/jats:sup> mice with activated Wnt signaling and NP models treated with Wnt signaling inhibitor, indocyanine green-001 (ICG-001). EMT markers and Wnt signaling-associated mediators were analysed using human sinonasal tissues from control subjects and CRSwNP patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Apc<jats:sup>Min\/+<\/jats:sup> mice-induced NPs exhibited more frequent polypoid lesions and upregulation of Wnt-related molecules, including nuclear \u03b2-catenin, WNT3A and cyclin D1. Markers of EMT were significantly overexpressed in the Apc<jats:sup>Min\/+<\/jats:sup> NP mice (p&lt;0.001 for E-cadherin and \u03b1-smooth muscle actin), and interleukin (IL)-17A<jats:sup>+<\/jats:sup> cells and neutrophilic infiltration were increased in Apc<jats:sup>Min\/+<\/jats:sup> NP mice (p&lt;0.001). Inhibition of Wnt signaling via ICG-001 resulted in significantly decreased nasal polypoid lesions (p&lt;0.001), EMT-related markers (p=0.019 for E-cadherin and p=0.002 for vimentin) and the mRNA levels of IL-4 (p&lt;0.001) and IL-17A (p=0.004) compared with the positive control group. Finally, nuclear \u03b2-catenin (p=0.042) was significantly increased compared with the control, and the expression levels of Wnt ligands and receptors were upregulated in human NP tissues (p=0.045 for WNT3A and p=0.042 for FZD2), suggesting increased Wnt signaling and EMT in CRSwNP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Wnt signaling may contribute to the pathogenesis of NPs through EMT. Therefore, inhibition of Wnt signaling may be a potential therapeutic strategy for patients with CRSwNP.<\/jats:p><\/jats:sec>","DOI":"10.1136\/thoraxjnl-2019-213916","type":"journal-article","created":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T21:27:53Z","timestamp":1602019673000},"page":"982-993","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Effects of Wnt signaling on epithelial to mesenchymal transition in chronic rhinosinusitis with nasal polyp"],"prefix":"10.1136","volume":"75","author":[{"given":"Jun-Sang","family":"Bae","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwanghui","family":"Ryu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hye","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun Hee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun Hee","family":"Rhee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Jun","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5166-3072","authenticated-orcid":false,"given":"Dae Woo","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suha","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phil-Sang","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4038-9992","authenticated-orcid":false,"given":"Hyun-Woo","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1331-364X","authenticated-orcid":false,"given":"Ji-Hun","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,10,6]]},"reference":[{"key":"2020101607253567000_75.11.982.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.10.009"},{"key":"2020101607253567000_75.11.982.2","doi-asserted-by":"publisher","DOI":"10.4193\/Rhino50E2"},{"key":"2020101607253567000_75.11.982.3","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/cea.12472","article-title":"Pathogenesis of nasal polyposis","volume":"45","author":"Hulse","year":"2015","journal-title":"Clin Exp Allergy"},{"key":"2020101607253567000_75.11.982.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.05.052"},{"key":"2020101607253567000_75.11.982.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.04.045"},{"key":"2020101607253567000_75.11.982.6","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201109-1706OC"},{"key":"2020101607253567000_75.11.982.7","doi-asserted-by":"publisher","DOI":"10.1111\/all.12503"},{"key":"2020101607253567000_75.11.982.8","doi-asserted-by":"publisher","DOI":"10.1159\/000147748"},{"key":"2020101607253567000_75.11.982.9","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3758"},{"key":"2020101607253567000_75.11.982.10","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200320530"},{"key":"2020101607253567000_75.11.982.11","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-052016-100401"},{"key":"2020101607253567000_75.11.982.12","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00224"},{"key":"2020101607253567000_75.11.982.13","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1165\/rcmb.2016-0024OC","article-title":"Wnt signaling in chronic rhinosinusitis with nasal polyps","volume":"56","author":"B\u00f6scke","year":"2017","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2020101607253567000_75.11.982.14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-2042.2007.01866.x"},{"key":"2020101607253567000_75.11.982.15","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-4135"},{"key":"2020101607253567000_75.11.982.16","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1205822109"},{"key":"2020101607253567000_75.11.982.17","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2008-0485TR"},{"key":"2020101607253567000_75.11.982.18","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2016-209753"},{"key":"2020101607253567000_75.11.982.19","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/resp.12882","article-title":"Transforming growth factor (TGF) \u03b2\n                  1\n                and Smad signalling pathways: A likely key to EMT-associated COPD pathogenesis","volume":"22","author":"Mahmood","year":"2017","journal-title":"Respirology"},{"key":"2020101607253567000_75.11.982.20","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200811-1730OC"},{"key":"2020101607253567000_75.11.982.21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.10.4482"},{"key":"2020101607253567000_75.11.982.22","doi-asserted-by":"publisher","DOI":"10.1126\/science.2296722"},{"key":"2020101607253567000_75.11.982.23","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2016-208772"},{"key":"2020101607253567000_75.11.982.24","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.jaci.2015.07.026","article-title":"Sirtuin 1 attenuates nasal polypogenesis by suppressing epithelial-to-mesenchymal transition","volume":"137","author":"Lee","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"2020101607253567000_75.11.982.25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0404875101"},{"key":"2020101607253567000_75.11.982.26","doi-asserted-by":"crossref","first-page":"148","DOI":"10.18632\/oncotarget.6653","article-title":"The role of TRPV1 in the CD4+ T cell-mediated inflammatory response of allergic rhinitis","volume":"7","author":"Samivel","year":"2016","journal-title":"Oncotarget"},{"key":"2020101607253567000_75.11.982.27","doi-asserted-by":"crossref","first-page":"359","DOI":"10.4142\/jvs.2017.18.3.359","article-title":"Evaluation of expression of the Wnt signaling components in canine mammary tumors via RT\n                  2\n                Profiler PCR Array and immunochemistry assays","volume":"18","author":"Yu","year":"2017","journal-title":"J Vet Sci"},{"key":"2020101607253567000_75.11.982.28","first-page":"183","article-title":"Staging in rhinosinusitus","volume":"31","author":"Lund","year":"1993","journal-title":"Rhinology"},{"key":"2020101607253567000_75.11.982.29","doi-asserted-by":"publisher","DOI":"10.1016\/S0194-5998(97)70005-6"},{"key":"2020101607253567000_75.11.982.30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-4486.2009.01995.x"},{"key":"2020101607253567000_75.11.982.31","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1016\/j.jaci.2015.01.003","article-title":"Il-25 as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis","volume":"135","author":"Shin","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"2020101607253567000_75.11.982.32","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2006.10.001"},{"key":"2020101607253567000_75.11.982.33","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgp125"},{"key":"2020101607253567000_75.11.982.34","doi-asserted-by":"publisher","DOI":"10.1172\/JCI61216"},{"key":"2020101607253567000_75.11.982.35","first-page":"3431","article-title":"Wnt\/\u03b2-catenin signaling pathway regulates asthma airway remodeling by influencing the expression of c-Myc and cyclin D1 via the p38 MAPK-dependent pathway","volume":"18","author":"Jia","year":"2019","journal-title":"Exp Ther Med"},{"key":"2020101607253567000_75.11.982.36","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9478542"},{"key":"2020101607253567000_75.11.982.37","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00172.2005"},{"key":"2020101607253567000_75.11.982.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2010.02.011"},{"key":"2020101607253567000_75.11.982.39","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.10.018"},{"key":"2020101607253567000_75.11.982.40","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1002\/alr.22199","article-title":"Nasal polyp fibroblasts modulate epithelial characteristics via Wnt signaling","volume":"8","author":"Dobzanski","year":"2018","journal-title":"Int Forum Allergy Rhinol"},{"key":"2020101607253567000_75.11.982.41","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2012-201667"},{"key":"2020101607253567000_75.11.982.42","doi-asserted-by":"crossref","DOI":"10.1038\/emm.2015.91","article-title":"The Wnt\/\u03b2-catenin signaling pathway regulates the development of airway remodeling in patients with asthma","volume":"47","author":"Kwak","year":"2015","journal-title":"Exp Mol Med"},{"key":"2020101607253567000_75.11.982.43","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/s41586-018-0449-8","article-title":"Allergic inflammatory memory in human respiratory epithelial progenitor cells","volume":"560","author":"Ordovas-Montanes","year":"2018","journal-title":"Nature"},{"key":"2020101607253567000_75.11.982.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.05.012"},{"key":"2020101607253567000_75.11.982.45","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/j.bbadis.2017.12.001","article-title":"Inhibition of canonical Wnt signaling pathway by \u03b2-catenin\/CBP inhibitor ICG-001 ameliorates liver fibrosis in vivo through suppression of stromal CXCL12","volume":"1864","author":"Akcora","year":"2018","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"2020101607253567000_75.11.982.46","doi-asserted-by":"crossref","first-page":"14","DOI":"10.4103\/jpp.JPP_153_16","article-title":"Indocyanine green-001 (ICG-001) attenuates wnt\/\u03b2-catenin-induces myocardial injury following sepsis","volume":"8","author":"Yousif","year":"2017","journal-title":"J Pharmacol Pharmacother"},{"key":"2020101607253567000_75.11.982.47","doi-asserted-by":"crossref","first-page":"27300","DOI":"10.18632\/oncotarget.15934","article-title":"The \u03b2-catenin\/CBP-antagonist ICG-001 inhibits pediatric glioma tumorigenicity in a Wnt-independent manner","volume":"8","author":"Wiese","year":"2017","journal-title":"Oncotarget"},{"key":"2020101607253567000_75.11.982.48","doi-asserted-by":"crossref","first-page":"507","DOI":"10.4168\/aair.2020.12.3.507","article-title":"Role of IL-17A in chronic rhinosinusitis with nasal polyp","volume":"12","author":"Ryu","year":"2020","journal-title":"Allergy Asthma Immunol Res"},{"key":"2020101607253567000_75.11.982.49","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2009.04.013"},{"key":"2020101607253567000_75.11.982.50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025450"},{"key":"2020101607253567000_75.11.982.51","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1165\/rcmb.2016-0307TR","article-title":"Transforming growth factor \u03b21 function in airway remodeling and hyperresponsiveness. The missing link?","volume":"56","author":"Ojiaku","year":"2017","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2020101607253567000_75.11.982.52","first-page":"1169","article-title":"Interleukin-17-Induced EMT promotes lung cancer cell migration and invasion via NF-\u03baB\/ZEB1 signal pathway","volume":"5","author":"Gu","year":"2015","journal-title":"Am J Cancer Res"},{"key":"2020101607253567000_75.11.982.53","article-title":"Interleukin-17 induces human alveolar epithelial to mesenchymal cell transition via the TGF-\u03b21 mediated Smad2\/3 and ERK1\/2 activation","volume":"12","author":"Wang","year":"2017","journal-title":"PLoS One"},{"key":"2020101607253567000_75.11.982.54","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1002\/1878-0261.12306","article-title":"Il-17A promotes the invasion-metastasis cascade via the Akt pathway in hepatocellular carcinoma","volume":"12","author":"Xu","year":"2018","journal-title":"Mol Oncol"},{"key":"2020101607253567000_75.11.982.55","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1093\/infdis\/jiy158","article-title":"Pulmonary colonization resistance to pathogens via noncanonical Wnt and interleukin-17A by intranasal Pep27 mutant immunization","volume":"217","author":"Kim","year":"2018","journal-title":"J Infect Dis"},{"key":"2020101607253567000_75.11.982.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2015.12.1324"},{"key":"2020101607253567000_75.11.982.57","doi-asserted-by":"crossref","first-page":"337","DOI":"10.21053\/ceo.2019.00654","article-title":"Neutrophils as a protagonist and target in chronic rhinosinusitis","volume":"12","author":"Wang","year":"2019","journal-title":"Clin Exp Otorhinolaryngol"},{"key":"2020101607253567000_75.11.982.58","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1016\/j.jaci.2019.06.023","article-title":"Cross-talk between TH 2 and TH 17 pathways in patients with chronic rhinosinusitis with nasal polyps","volume":"144","author":"Wang","year":"2019","journal-title":"J Allergy Clin Immunol"}],"container-title":["Thorax"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/thoraxjnl-2019-213916","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T14:28:52Z","timestamp":1602858532000},"score":1,"resource":{"primary":{"URL":"https:\/\/thorax.bmj.com\/lookup\/doi\/10.1136\/thoraxjnl-2019-213916"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,6]]},"references-count":58,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,10,16]]},"published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1136\/thoraxjnl-2019-213916"],"URL":"https:\/\/doi.org\/10.1136\/thoraxjnl-2019-213916","relation":{},"ISSN":["0040-6376","1468-3296"],"issn-type":[{"value":"0040-6376","type":"print"},{"value":"1468-3296","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,6]]}}}