{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:16:52Z","timestamp":1792804612271,"version":"4.5.0"},"reference-count":130,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T00:00:00Z","timestamp":1610928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"by the Ministry of Science and Technology and the Ministry of Science, ICT &amp; Future Planning","award":["2017R1A2B2003575"],"award-info":[{"award-number":["2017R1A2B2003575"]}]},{"name":"the Ministry of Science and Technology and the Ministry of Science, ICT &amp; Future Planning","award":["NRF-2020R1A2C1006398"],"award-info":[{"award-number":["NRF-2020R1A2C1006398"]}]},{"name":"the Ministry of Science and ICT","award":["2020R1C1C1012288"],"award-info":[{"award-number":["2020R1C1C1012288"]}],"id":[{"id":"https:\/\/ror.org\/01wpjm123","id-type":"ROR","asserted-by":"crossref"}]},{"name":"(Institute for Information &amp; Communications Technology Planning &amp; Evaluation","award":["IITP-2020-0018190011001"],"award-info":[{"award-number":["IITP-2020-0018190011001"]}],"id":[{"id":"https:\/\/ror.org\/01g0hqq23","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Korea Health Industry Development Institute (KHIDI), and the Ministry of Health &amp; Welfare","award":["HI17C0387"],"award-info":[{"award-number":["HI17C0387"]}],"id":[{"id":"https:\/\/ror.org\/00vxgjw72","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chronic rhinosinusitis (CRS) is a chronic inflammatory condition of the nasal and paranasal sinus mucosa that affects up to 10% of the population worldwide. CRS is the most representative disease of the upper respiratory tract where airway remodeling occurs, including epithelial damage, thickening of the basement membrane, fibrosis, goblet cell hyperplasia, subepithelial edema, and osteitis. CRS is divided into two phenotypes according to the presence or absence of nasal polyps: CRS with nasal polyp (CRSwNP) and CRS without nasal polyps (CRSsNP). Based on the underlying pathophysiologic mechanism, CRS is also classified as eosinophilic CRS and non-eosinophilic CRS, owing to Type 2 T helper (Th2)-based inflammation and Type 1 T helper (Th1)\/Type 17 T helper (Th17) skewed immune response, respectively. Differences in tissue remodeling in CRS are suggested to be based on the clinical phenotype and endotypes; this is because fibrosis is prominent in CRSsNP, whereas edematous changes occur in CRSwNP, especially in the eosinophilic type. This review aims to summarize the latest information on the different mechanisms of airway remodeling in CRS according to distinct endotypes.<\/jats:p>","DOI":"10.3390\/ijms22020910","type":"journal-article","created":{"date-parts":[[2021,1,19]],"date-time":"2021-01-19T04:55:31Z","timestamp":1611032131000},"page":"910","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Advances in the Knowledge of the Underlying Airway Remodeling Mechanisms in Chronic Rhinosinusitis Based on the Endotypes: A Review"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9799-662X","authenticated-orcid":false,"given":"Kijeong","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology-Head &amp; Neck Surgery, College of Medicine, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1491-9889","authenticated-orcid":false,"given":"Junhu","family":"Tai","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head &amp; Neck Surgery, College of Medicine, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Hag","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head &amp; Neck Surgery, College of Medicine, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head &amp; Neck Surgery, College of Medicine, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4193\/Rhin20.401","article-title":"European Position Paper on Rhinosinusitis and Nasal Polyps 2020","volume":"58","author":"Fokkens","year":"2020","journal-title":"Rhinology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11882-020-00916-6","article-title":"Phenotypes in Chronic Rhinosinusitis","volume":"20","author":"McCormick","year":"2020","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.otohns.2004.09.067","article-title":"Otolaryngology-Head and Neck Surgery","volume":"131","author":"Meltzer","year":"2004","journal-title":"Otolaryngol. Neck Surg."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1016\/j.jaci.2013.02.036","article-title":"Endotypes and phenotypes of chronic rhinosinusitis: A PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology","volume":"131","author":"Akdis","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.jaip.2016.05.004","article-title":"Phenotypes and Emerging Endotypes of Chronic Rhinosinusitis","volume":"4","author":"Bachert","year":"2016","journal-title":"J. Allergy Clin. Immunol. Pr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1111\/j.1398-9995.2006.01225.x","article-title":"Differentiation of chronic sinus diseases by measurement of inflammatory mediators","volume":"61","author":"Claeys","year":"2006","journal-title":"Allergy"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.amjoto.2018.03.020","article-title":"Nasal polyposis pathophysiology: Endotype and phenotype open issues","volume":"39","author":"Brescia","year":"2018","journal-title":"Am. J. Otolaryngol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.jaci.2009.05.017","article-title":"Distinct immunopathologic characteristics of various types of chronic rhinosinusitis in adult Chinese","volume":"124","author":"Cao","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"121","DOI":"10.5415\/apallergy.2017.7.3.121","article-title":"Classification of chronic rhinosinusitis according to a nasal polyp and tissue eosinophilia: Limitation of current classification system for Asian population","volume":"7","author":"Cho","year":"2017","journal-title":"Asia Pac. Allergy"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.jaci.2020.04.040","article-title":"Type 2 inflammation in chronic rhinosinusitis without nasal polyps: Another relevant endotype","volume":"146","author":"Delemarre","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1172\/JCI45961","article-title":"The three R\u2019s of lung health and disease: Repair, remodeling, and regeneration","volume":"121","author":"Beers","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"191","DOI":"10.3389\/fmed.2020.00191","article-title":"Airway Remodeling in Asthma","volume":"7","author":"Hough","year":"2020","journal-title":"Front. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1111\/all.13373","article-title":"Upper and lower airway remodelling mechanisms in asthma, allergic rhinitis and chronic rhinosinusitis: The one airway concept revisited","volume":"73","author":"Samitas","year":"2017","journal-title":"Allergy"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1097\/ACI.0b013e32835ad09e","article-title":"Mucosal remodeling and reversibility in chronic rhinosinusitis","volume":"13","author":"Bassiouni","year":"2013","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1111\/coa.13455","article-title":"Understanding and clinical relevance of chronic rhinosinusitis endotypes","volume":"44","author":"Husain","year":"2019","journal-title":"Clin. Otolaryngol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1016\/j.jaci.2016.05.041","article-title":"Diversity of T H cytokine profiles in patients with chronic rhinosinusitis: A multicenter study in Europe, Asia, and Oceania","volume":"138","author":"Wang","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.jaci.2016.06.063","article-title":"Heterogeneous inflammatory patterns in chronic rhinosinusitis without nasal polyps in Chicago, Illinois","volume":"139","author":"Tan","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1016\/j.jaci.2015.12.1324","article-title":"Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers","volume":"137","author":"Tomassen","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1016\/j.jaci.2018.02.002","article-title":"Identification of clinically relevant chronic rhinosinusitis endotypes using cluster analysis of mucus cytokines","volume":"141","author":"Turner","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1146\/annurev-pathol-052016-100401","article-title":"Immunopathogenesis of Chronic Rhinosinusitis and Nasal Polyposis","volume":"12","author":"Schleimer","year":"2017","journal-title":"Annu. Rev. Pathol. Mech. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1016\/j.jaip.2019.05.009","article-title":"Associations Between Inflammatory Endotypes and Clinical Presentations in Chronic Rhinosinusitis","volume":"7","author":"Stevens","year":"2019","journal-title":"J. Allergy Clin. Immunol. Pr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/2643297","article-title":"Release of Type 2 Cytokines by Epithelial Cells of Nasal Polyps","volume":"2016","author":"Boita","year":"2016","journal-title":"J. Immunol. Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/ni.2617","article-title":"TH2, allergy and group 2 innate lymphoid cells","volume":"14","author":"Kim","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.4049\/jimmunol.178.3.1396","article-title":"Induction of IL-4 expression in CD4(+) T cells by thymic stromal lymphopoietin","volume":"178","author":"Omori","year":"2007","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ejphar.2015.04.047","article-title":"IL-33 and Thymic Stromal Lymphopoietin in mast cell functions","volume":"778","author":"Saluja","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/S0091-6749(97)70276-8","article-title":"The relative contribution of IL-4 and IL-13 to human IgE synthesis induced by activated CD4 or CD8 T cells","volume":"100","author":"Punnonen","year":"1997","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S0091-6749(95)70298-9","article-title":"Evidence for distinct cytokine expression in allergic versus nonallergic chronic sinusitis","volume":"96","author":"Hamilos","year":"1995","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jaci.2011.08.021","article-title":"Increased expression of CC chemokine ligand 18 in patients with chronic rhinosinusitis with nasal polyps","volume":"129","author":"Poposki","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.jaci.2011.03.017","article-title":"Increased expression of the chemokine CCL23 in eosinophilic chronic rhinosinusitis with nasal polyps","volume":"128","author":"Poposki","year":"2011","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s11882-019-0853-7","article-title":"The Role of Staphylococcus aureus in Patients with Chronic Sinusitis and Nasal Polyposis","volume":"19","author":"Vickery","year":"2019","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1164\/rccm.201710-2112OC","article-title":"Staphylococcus aureusInduces a Mucosal Type 2 Immune Response via Epithelial Cell\u2013derived Cytokines","volume":"198","author":"Lan","year":"2018","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1007\/s00405-015-3816-1","article-title":"Different activations of toll-like receptors and antimicrobial peptides in chronic rhinosinusitis with or without nasal polyposis","volume":"273","author":"Hirschberg","year":"2016","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_33","first-page":"209","article-title":"The Biology and Functions of Th22 Cells","volume":"841","author":"Jia","year":"2014","journal-title":"Cannabinoids Neuropsychiatr. Disord."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1007\/s004050100363","article-title":"Elevated levels of myeloperoxidase, pro-inflammatory cytokines and chemokines in naturally acquired upper respiratory tract infections","volume":"258","author":"Bachert","year":"2001","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s10875-019-00684-7","article-title":"Regulatory T Cells: The Many Faces of Foxp3","volume":"39","author":"Georgiev","year":"2019","journal-title":"J. Clin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"345","DOI":"10.2500\/ajra.2017.31.4472","article-title":"The Role of Regulatory T Cells in the Regulation of Upper Airway Inflammation","volume":"31","author":"Palmer","year":"2017","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.jaci.2009.04.013","article-title":"TGF-\u03b2 signaling and collagen deposition in chronic rhinosinusitis","volume":"124","author":"DeRycke","year":"2009","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1016\/j.jaci.2015.10.009","article-title":"Chronic rhinosinusitis pathogenesis","volume":"136","author":"Stevens","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/all.12064","article-title":"Features of airway remodeling in different types of Chinese chronic rhinosinusitis are associated with inflammation patterns","volume":"68","author":"Shi","year":"2012","journal-title":"Allergy"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1895","DOI":"10.1097\/01.mlg.0000147917.43615.c0","article-title":"Molecular and Cellular Staging for the Severity of Chronic Rhinosinusitis","volume":"114","author":"Kountakis","year":"2004","journal-title":"Laryngoscope"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1016\/j.jaci.2020.04.010","article-title":"Epithelial barriers in allergy and asthma","volume":"145","author":"Hellings","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.anai.2020.01.018","article-title":"Epithelial cell function and remodeling in nasal polyposis","volume":"124","author":"Bankova","year":"2020","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1513\/pats.200907-067DP","article-title":"The Role of the Epithelium in Airway Remodeling in Asthma","volume":"6","author":"Davies","year":"2009","journal-title":"Proc. Am. Thorac. Soc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"60","DOI":"10.4110\/in.2017.17.1.60","article-title":"Immune Cell Responses and Mucosal Barrier Disruptions in Chronic Rhinosinusitis","volume":"17","author":"Khalmuratova","year":"2017","journal-title":"Immune Netw."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1001\/archotol.130.6.747","article-title":"Up-regulation of MUC5AC and MUC5B Mucin Genes in Chronic Rhinosinusitis","volume":"130","author":"Kim","year":"2004","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1172\/JCI39104","article-title":"The basics of epithelial-mesenchymal transition","volume":"119","author":"Kalluri","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1164\/rccm.200811-1730OC","article-title":"Induction of Epithelial\u2013Mesenchymal Transition in Primary Airway Epithelial Cells from Patients with Asthma by Transforming Growth Factor-\u03b21","volume":"180","author":"Hackett","year":"2009","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2009.11.007","article-title":"Epithelial-Mesenchymal Transitions in Development and Disease","volume":"139","author":"Thiery","year":"2009","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.jaci.2003.08.009","article-title":"Features of airway remodeling and eosinophilic inflammation in chronic rhinosinusitis","volume":"112","author":"Ponikau","year":"2003","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"275","DOI":"10.4193\/Rhin08.109","article-title":"Relationship between epithelial damage or basement membrane thickness and eosinophilic infiltration in nasal polyps with chronic rhinosinusitis","volume":"47","author":"Saitoh","year":"2009","journal-title":"Rhinol. J."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"8061","DOI":"10.1038\/s41598-019-44627-z","article-title":"Eosinophil extracellular trap formation is closely associated with disease severity in chronic rhinosinusitis regardless of nasal polyp status","volume":"9","author":"Hwang","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/j.jaci.2012.05.052","article-title":"Defective epithelial barrier in chronic rhinosinusitis: The regulation of tight junctions by IFN-\u03b3 and IL-4","volume":"130","author":"Soyka","year":"2012","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"572749","DOI":"10.3389\/fcell.2020.572749","article-title":"Interleukin-13 Alters Tight Junction Proteins Expression Thereby Compromising Barrier Function and Dampens Rhinovirus Induced Immune Responses in Nasal Epithelium","volume":"8","author":"Huang","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1111\/cea.13760","article-title":"Staphylococcus aureus enterotoxin B disrupts nasal epithelial barrier integrity","volume":"51","author":"Martens","year":"2021","journal-title":"Clin. Exp. Allergy"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"538","DOI":"10.3389\/fcimb.2017.00538","article-title":"Emerging Role of Proteases in the Pathogenesis of Chronic Rhinosinusitis with Nasal Polyps","volume":"7","author":"Wu","year":"2018","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1089\/jir.2015.0058","article-title":"Epithelial Cell-Derived Cytokines Contribute to the Pathophysiology of Eosinophilic Chronic Rhinosinusitis","volume":"36","author":"Kouzaki","year":"2016","journal-title":"J. Interf. Cytokine Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/cea.12644","article-title":"Role of IFN-\u03b3, IL-13, and IL-17 on mucociliary differentiation of nasal epithelial cells in chronic rhinosinusitis with nasal polyps","volume":"46","author":"Jiao","year":"2016","journal-title":"Clin. Exp. Allergy"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.cyto.2016.10.010","article-title":"Interleukin-33 induces mucin gene expression and goblet cell hyperplasia in human nasal epithelial cells","volume":"90","author":"Ishinaga","year":"2017","journal-title":"Cytokine"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1016\/j.jaci.2015.05.024","article-title":"Increased expression of the epithelial anion transporter pendrin\/SLC26A4 in nasal polyps of patients with chronic rhinosinusitis","volume":"136","author":"Seshadri","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1002\/wdev.86","article-title":"The TGFbeta Superfamily Signaling Pathway","volume":"2","author":"Weiss","year":"2013","journal-title":"Wiley Interdiscip. Rev. Dev. Boil."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Park, I.-H., Kang, J.-H., Shin, J.-M., and Lee, H.-M. (2016). Trichostatin A Inhibits Epithelial Mesenchymal Transition Induced by TGF-\u03b21 in Airway Epithelium. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162058"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1159\/000497829","article-title":"TGF-\u03b21 Induces Epithelial-Mesenchymal Transition of Chronic Sinusitis with Nasal Polyps through MicroRNA-21","volume":"179","author":"Li","year":"2019","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_63","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":"Ms","year":"2018","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/s41385-019-0149-1","article-title":"The IFN-\u03b3\u2013p38, ERK kinase axis exacerbates neutrophilic chronic rhinosinusitis by inducing the epithelial-to-mesenchymal transition","volume":"12","author":"Lee","year":"2019","journal-title":"Mucosal Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1164\/rccm.201109-1706OC","article-title":"Hypoxia-inducible Factor 1 Mediates Nasal Polypogenesis by Inducing Epithelial-to-Mesenchymal Transition","volume":"185","author":"Shin","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_66","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":"ref_67","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.jaci.2016.06.064","article-title":"MUC4 impairs the anti-inflammatory effects of corticosteroids in patients with chronic rhinosinusitis with nasal polyps","volume":"139","author":"Milara","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Xia, W., Bai, J., Wu, X., Wei, Y., Feng, S., Li, L., Zhang, J., Xiong, G., Fan, Y., and Shi, J. (2014). Interleukin-17A Promotes MUC5AC Expression and Goblet Cell Hyperplasia in Nasal Polyps via the Act1-Mediated Pathway. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098915"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1177\/1945892419871798","article-title":"Human Neutrophil Elastase Induces MUC5AC Overexpression in Chronic Rhinosinusitis Through miR-146a","volume":"34","author":"Yan","year":"2020","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"641","DOI":"10.3109\/00016489.2016.1144145","article-title":"Human neutrophil elastase induces MUC5AC overexpression in chronic rhinosinusitis through tumour necrosis factor-\u03b1 converting enzyme","volume":"136","author":"Luo","year":"2016","journal-title":"Acta Oto-Laryngol."},{"key":"ref_71","first-page":"1199","article-title":"Relationship of TLR2, TLR4 and tissue remodeling in chronic rhinosinusitis","volume":"8","author":"Wang","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1097\/00005537-200310000-00027","article-title":"IL-11 and IL-17 expression in nasal polyps: Relationship to collagen deposition and suppression by intranasal fluticasone propionate","volume":"113","author":"Molet","year":"2003","journal-title":"Laryngoscope"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"651","DOI":"10.2500\/ajr.2007.21.3096","article-title":"Mucosal Remodeling in Chronic Rhinosinusitis","volume":"21","author":"Rehl","year":"2007","journal-title":"Am. J. Rhinol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1097\/00005537-200303000-00004","article-title":"Inflammation and Remodeling of the Sinus Mucosa in Children and Adults with Chronic Sinusitis","volume":"113","author":"Sobol","year":"2003","journal-title":"Laryngoscope"},{"key":"ref_75","first-page":"1975","article-title":"A histopathological study: Chronic rhinosinusitis in adolescents versus adults","volume":"89","author":"Zang","year":"2009","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1097\/MLG.0b013e318030aca6","article-title":"Metalloproteinase Function in Chronic Rhinosinusitis with Nasal Polyposis","volume":"117","author":"Kostamo","year":"2007","journal-title":"Laryngoscope"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1165\/ajrcmb.20.6.f151","article-title":"Matrix Metalloproteinases","volume":"20","author":"Shapiro","year":"1999","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_78","first-page":"684","article-title":"The role of MMP-9 and TIMP-1 in nasal polyp formation","volume":"138","author":"Kahveci","year":"2008","journal-title":"Swiss Med. Wkly."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"151","DOI":"10.3109\/00016488409130975","article-title":"Mucus Production in Chronic Maxillary Sinusitis: A Quantitative Histopathological Study","volume":"97","author":"Tos","year":"1984","journal-title":"Acta Oto-Laryngol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1080\/00016480510027538","article-title":"Mucin gene expression in nasal polyps","volume":"125","author":"Ali","year":"2005","journal-title":"Acta Oto-Laryngol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1002\/alr.22065","article-title":"Submucosal gland mucus strand velocity is decreased in chronic rhinosinusitis","volume":"8","author":"Tipirneni","year":"2018","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1097\/00005537-200012000-00023","article-title":"Bone Involvement in Sinusitis: An Apparent Pathway for the Spread of Disease","volume":"110","author":"Perloff","year":"2000","journal-title":"Laryngoscope"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1159\/000024209","article-title":"Distinct expression of RANTES and GM-CSF by lipopolysaccharide in human nasal fibroblasts but not in other airway fibroblasts","volume":"119","author":"Nonaka","year":"1999","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.amjoto.2019.03.014","article-title":"Histopathologic analysis in chronic rhinosinusitis: Impact on quality of life outcomes","volume":"40","author":"Wang","year":"2019","journal-title":"Am. J. Otolaryngol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"422","DOI":"10.2500\/ajra.2010.24.3509","article-title":"Staphylococcus Aureus Increases Cytokine and Matrix Metalloproteinase Expression in Nasal Mucosae of Patients with Chronic Rhinosinusitis and Nasal Polyps","volume":"24","author":"Wang","year":"2010","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/j.1398-9995.2006.01255.x","article-title":"Relationship between matrix metalloproteinases MMP-2, MMP-9, tissue inhibitor of matrix metalloproteinases-1 and IL-5, IL-8 in nasal polyps","volume":"62","author":"Chen","year":"2007","journal-title":"Allergy"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1177\/194589240401800502","article-title":"Transforming growth factor beta1 in nasal remodeling: Differences between chronic rhinosinusitis and nasal polyposis","volume":"18","author":"Watelet","year":"2004","journal-title":"Am. J. Rhinol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1046\/j.1398-9995.2003.00364.x","article-title":"Matrix metalloproteinases MMP-7, MMP-9 and their tissue inhibitor TIMP-1: Expression in chronic sinusitis vs nasal polyposis","volume":"59","author":"Watelet","year":"2004","journal-title":"Allergy"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.otohns.2008.04.032","article-title":"The expression of MMP-2, MMP-7, MMP-9, and TIMP-1 in chronic rhinosinusitis and nasal polyposis","volume":"139","author":"Can","year":"2008","journal-title":"Otolaryngol. Neck Surg."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"421","DOI":"10.4168\/aair.2015.7.5.421","article-title":"Chronic Rhinosinusitis and the Coagulation System","volume":"7","author":"Kim","year":"2015","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.jaci.2013.02.003","article-title":"Increased expression of factor XIII-A in patients with chronic rhinosinusitis with nasal polyps","volume":"132","author":"Takabayashi","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1164\/rccm.201207-1292OC","article-title":"Excessive Fibrin Deposition in Nasal Polyps Caused by Fibrinolytic Impairment through Reduction of Tissue Plasminogen Activator Expression","volume":"187","author":"Takabayashi","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2500\/ajra.2011.25.3537","article-title":"The Expression of Fibrinolytic Components in Chronic Paranasal Sinus Disease","volume":"25","author":"Sejima","year":"2011","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/all.13489","article-title":"Th2 cytokines orchestrate the secretion of MUC 5 AC and MUC 5B in IL -5-positive chronic rhinosinusitis with nasal polyps","volume":"74","author":"Zhang","year":"2019","journal-title":"Allergy"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.jaci.2010.02.023","article-title":"Expression of TGF, matrix metalloproteinases, and tissue inhibitors in Chinese chronic rhinosinusitis","volume":"125","author":"Li","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_96","first-page":"1","article-title":"Chronic Rhinosinusitis without Nasal Polyps in Asian Patients Shows Mixed Inflammatory Patterns and Neutrophil-Related Disease Severity","volume":"2019","author":"Kim","year":"2019","journal-title":"Mediat. Inflamm."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"201","DOI":"10.4168\/aair.2019.11.2.201","article-title":"Comparison Between Signature Cytokines of Nasal Tissues in Subtypes of Chronic Rhinosinusitis","volume":"11","author":"Park","year":"2019","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"581","DOI":"10.4193\/Rhin19.319","article-title":"Microarray analysis of primary epithelial and fibroblast cells in chronic rhinosinusitis without nasal polyps","volume":"58","author":"Ball","year":"2020","journal-title":"Rhinology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s11882-019-0855-5","article-title":"Osteitis in Chronic Rhinosinusitis","volume":"19","author":"Snidvongs","year":"2019","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_100","first-page":"299","article-title":"Osteitic bone: A surrogate marker of eosinophilia in chronic rhinosinusitis","volume":"50","author":"Snidvongs","year":"2012","journal-title":"Rhinol. J."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.otohns.2006.04.005","article-title":"CT analysis and histopathology of bone remodeling in patients with chronic rhinosinusitis","volume":"135","author":"Cho","year":"2006","journal-title":"Otolaryngol. Neck Surg."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/j.bjorl.2015.03.003","article-title":"Osteitis and mucosal inflammation in a rabbit model of sinusitis","volume":"81","author":"Dolci","year":"2015","journal-title":"Braz. J. Otorhinolaryngol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3109\/00016489409124322","article-title":"The Inflammatory Response of the Sinus and Nasal Mucosa During Sinusitis: Implications for Research and Therapy","volume":"114","author":"Norlander","year":"1994","journal-title":"Acta Oto-Laryngol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/S0025-6196(11)60895-1","article-title":"Blood and Sputum Eosinophil Levels in Asthma and Their Relationship to Sinus Computed Tomographic Findings","volume":"83","author":"Mehta","year":"2008","journal-title":"Mayo Clin. Proc."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1002\/alr.21176","article-title":"P-glycoprotein is a marker of tissue eosinophilia and radiographic inflammation in chronic rhinosinusitis without nasal polyps","volume":"3","author":"Feldman","year":"2013","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.wjorl.2018.07.002","article-title":"P-glycoprotein and chronic rhinosinusitis","volume":"4","author":"Miyake","year":"2018","journal-title":"World J. Otorhinolaryngol. Head Neck Surg."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"99","DOI":"10.2500\/ajra.2014.28.4011","article-title":"Osteitis is Associated with P-Glycoprotein Overexpression in Patients with Chronic Sinusitis without Nasal Polyps","volume":"28","author":"Feldman","year":"2014","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_108","first-page":"E85","article-title":"Microarray analysis of the genes associated with osteitis in chronic rhinosinusitis","volume":"127","author":"Bleier","year":"2017","journal-title":"Laryngoscope"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1002\/lary.22148","article-title":"Tissue remodeling gene expression in a murine model of chronic rhinosinusitis","volume":"122","author":"Sautter","year":"2012","journal-title":"Laryngoscope"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"338","DOI":"10.3109\/00365513.2010.488698","article-title":"Expression of markers of activity in cultured human osteoblasts: Effects of interleukin-4 and interleukin-13","volume":"70","author":"Penno","year":"2010","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/j.jaci.2017.05.021","article-title":"Increased IL-13 expression is independently associated with neo-osteogenesis in patients with chronic rhinosinusitis","volume":"140","author":"Oue","year":"2017","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"306","DOI":"10.4168\/aair.2020.12.2.306","article-title":"Evaluation of Neo-Osteogenesis in Eosinophilic Chronic Rhinosinusitis Using a Nasal Polyp Murine Model","volume":"12","author":"Khalmuratova","year":"2020","journal-title":"Allergy, Asthma Immunol. Res."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.ebiom.2019.07.035","article-title":"Interleukin (IL)-13 and IL-17A contribute to neo-osteogenesis in chronic rhinosinusitis by inducing RUNX2","volume":"46","author":"Khalmuratova","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1951","DOI":"10.1097\/00005537-200211000-00008","article-title":"The Role of Bone in Chronic Rhinosinusitis","volume":"112","author":"Khalid","year":"2002","journal-title":"Laryngoscope"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1080\/00016489.2016.1252060","article-title":"Computed tomography and histopathological evaluation of osteitis in rabbit models with rhinosinusitis","volume":"137","author":"Dong","year":"2016","journal-title":"Acta Oto-Laryngol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/alr.21485","article-title":"Clinical predictors of neo-osteogenesis in patients with chronic rhinosinusitis","volume":"5","author":"Huang","year":"2015","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1002\/alr.22507","article-title":"Risk factors for neo-osteogenesis in cystic fibrosis and non\u2012cystic fibrosis chronic rhinosinusitis","volume":"10","author":"Karempelis","year":"2020","journal-title":"Int. Forum Allergy Rhinol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1002\/lary.24424","article-title":"Correlation between bacterial biofilms and osteitis in patients with chronic rhinosinusitis","volume":"124","author":"Dong","year":"2013","journal-title":"Laryngoscope"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"415","DOI":"10.4193\/Rhino09.087","article-title":"Inflammatory cytokines gene expression in bone tissue from patients with chronic rhinosinusitis- a preliminary study","volume":"48","author":"Tuszynska","year":"2010","journal-title":"Rhinol. J."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"e152","DOI":"10.2500\/ajra.2015.29.4241","article-title":"Differing Roles for TGF-\u03b2\/Smad Signaling in Osteitis in Chronic Rhinosinusitis with and without Nasal Polyps","volume":"29","author":"Wang","year":"2015","journal-title":"Am. J. Rhinol. Allergy"},{"key":"ref_121","first-page":"E158","article-title":"Corticosteroid treatment regulates mucosal remodeling in chronic rhinosinusitis with nasal polyps","volume":"125","author":"Picado","year":"2015","journal-title":"Laryngoscope"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1016\/j.jaci.2014.10.018","article-title":"Effect of budesonide transnasal nebulization in patients with eosinophilic chronic rhinosinusitis with nasal polyps","volume":"135","author":"Wang","year":"2015","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_123","first-page":"773","article-title":"[Effects of glucocorticoid on tissue remodeling of nasal mucosa of chronic rhinosinusitis with nasal polyposis after endoscopic surgery]","volume":"41","author":"Yu","year":"2006","journal-title":"Chin. J. Otorhinolaryngol. Head Neck Surg."},{"key":"ref_124","first-page":"369","article-title":"In vitro effects of doxycycline on inflammatory cytokines and gelatinases in chronic rhinosinusitis","volume":"26","author":"Sommer","year":"2012","journal-title":"In Vivo"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1111\/j.1524-475X.2008.00429.x","article-title":"Pilot study using doxycycline-releasing stents to ameliorate postoperative healing quality after sinus surgery","volume":"16","author":"Huvenne","year":"2008","journal-title":"Wound Repair Regen."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2787","DOI":"10.1128\/AAC.43.11.2787","article-title":"Differential Modulatory Effects of Clarithromycin on the Production of Cytokines by a Tumor","volume":"43","author":"Sassa","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12890-019-0952-1","article-title":"Efficacy of mepolizumab for patients with severe asthma and eosinophilic chronic rhinosinusitis","volume":"19","author":"Numata","year":"2019","journal-title":"BMC Pulm. Med."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.alit.2020.02.002","article-title":"The roles of IL-5 and anti-IL-5 treatment in eosinophilic diseases: Asthma, eosinophilic granulomatosis with polyangiitis, and eosinophilic chronic rhinosinusitis","volume":"69","author":"Nagase","year":"2020","journal-title":"Allergol. Int."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1172\/JCI17974","article-title":"Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics","volume":"112","author":"Phipps","year":"2003","journal-title":"J. Clin. Investig."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.iac.2019.12.007","article-title":"Personalized Medicine in Chronic Rhinosinusitis","volume":"40","author":"Bauer","year":"2020","journal-title":"Immunol. Allergy Clin. N. Am."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/2\/910\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:12:30Z","timestamp":1760159550000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/2\/910"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,18]]},"references-count":130,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["ijms22020910"],"URL":"https:\/\/doi.org\/10.3390\/ijms22020910","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,18]]}}}