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S100A9, a protein secreted by inflammatory cells, exhibits potent proinflammatory activity. However, its effect on HNE cell remodeling, such as squamous metaplasia, remains unclear. Therefore, this study aimed to determine the effects and underlying pathways of S100A9 on HNE cell remodeling and investigate its clinical implications in chronic rhinosinusitis (CRS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cultured HNE cells were treated with S100A9. Bulk RNA sequencing was performed to analyze gene ontology (GO). Ingenuity pathway analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were also analyzed. Additionally, immunohistochemistry and multiplex immunofluorescence were performed on tissue samples obtained from 60 patients, whose clinical informations were also reviewed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>GO enrichment analysis indicated that S100A9 induced tissue remodeling in HNE cells toward squamous metaplasia. IPA and KEGG commonly showed that S100A9 affected HNE cells associated with the IL\u201017 signaling pathway, including target molecules such as matrix metalloproteinase 1 (MMP1) and small proline\u2010rich protein 2A (SPRR2A). Squamous metaplasia with a marked expression of S100A9 was observed in 50% of CRS with nasal polyps (CRSwNPs). In addition, in multiplex immunofluorescence, the S100A9 in sub\u2010epithelium was co\u2010expressed with myeloperoxidase, a neutrophil marker, and MMP1 and SPRR2A were strongly expressed in epithelial remodeling. Clinically, the expression of S100A9 correlated with sino\u2010nasal outcome test\u201022 (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.294, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.022) and Lund\u2013Mackay scores (<jats:italic>r<\/jats:italic>\u00a0=\u00a00.348, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.006).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>S100A9 induces tissue remodeling in HNE cells. Its increased expression in CRSwNP, particularly squamous epithelium, correlates with disease severity. This suggests the clinical potential of S100A9 as a biomarker for CRS severity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alr.23460","type":"journal-article","created":{"date-parts":[[2024,10,5]],"date-time":"2024-10-05T12:24:33Z","timestamp":1728131073000},"page":"135-148","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["S100A9 induces tissue remodeling of human nasal epithelium in chronic rhinosinusitis with nasal polyp"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2389-0005","authenticated-orcid":false,"given":"Sang Hyeon","family":"Ahn","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Daejin Medical Center Bundang Jesaeng General Hospital  Seongnam South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Taek","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Daejin Medical 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