{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:47:57Z","timestamp":1792097277718,"version":"4.4.0"},"reference-count":24,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T00:00:00Z","timestamp":1735603200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","award":["RS-2024-00463105"],"award-info":[{"award-number":["RS-2024-00463105"]}],"id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Th2 inflammation and epithelial-mesenchymal transition (EMT) play crucial roles in the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNP). This study aimed to investigate the hypothesis that MMP-12, produced by M2 macrophages, induces EMT in nasal epithelial cells, thereby contributing to airway inflammation and remodeling in CRSwNP. The expression levels of MMP-12 were measured by RT-PCR in CRS nasal mucosa and THP-1 cells. mRNA and protein levels of E-cadherin, vimentin, \u03b1-SMA, and fibronectin were determined using RT-PCR, western blotting, and immunofluorescence staining in primary nasal epithelial cells and air-liquid interface culture. The expression of MMP-12 was significantly increased in CRSwNP and M2-like THP-1 cells. In co-culture with primary nasal epithelial cells and M2-like THP-1 cells, E-cadherin expression was inhibited, and fibronectin, vimentin, and \u03b1-SMA expression were increased. MMP-12 decreased E-cadherin but induced fibronectin, vimentin, and \u03b1-SMA mRNA and protein expression in primary nasal epithelial cells and air-liquid interface culture. MMP408, an MMP-12 inhibitor, inhibited EMT-related factors. These findings suggest that MMP-12 expression in M2 macrophages induces EMT in nasal epithelial cells and may contribute to the pathogenesis of CRSwNP.<\/jats:p>","DOI":"10.1371\/journal.pone.0313097","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T18:28:53Z","timestamp":1735669733000},"page":"e0313097","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Matrix metalloproteinase-12 by M2 macrophages induced epithelial to mesenchymal transition in chronic rhinosinusitis with nasal polyps"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3221-640X","authenticated-orcid":true,"given":"Joo-Hoo","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Min","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun-Woo","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Hoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Hoon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ok Sarah","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7011-6071","authenticated-orcid":true,"given":"Il-Ho","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,12,31]]},"reference":[{"issue":"4","key":"pone.0313097.ref001","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.jaip.2016.04.012","article-title":"Chronic Rhinosinusitis with Nasal Polyps","volume":"4","author":"WW Stevens","year":"2016","journal-title":"J Allergy Clin Immunol Pract"},{"issue":"3","key":"pone.0313097.ref002","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":"SW Cho","year":"2017","journal-title":"Asia Pac Allergy"},{"issue":"2","key":"pone.0313097.ref003","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1177\/0194599814528672","article-title":"Macrophage Infiltrate Is Elevated in CRSwNP Sinonasal Tissue Regardless of Atopic Status.","volume":"151","author":"CA Banks","year":"2014","journal-title":"Otolaryngol Head Neck Surg."},{"key":"pone.0313097.ref004","doi-asserted-by":"crossref","first-page":"110449","DOI":"10.1016\/j.intimp.2023.110449","article-title":"Overexpression of AXL on macrophages associates with disease severity and recurrence in chronic rhinosinusitis with nasal polyps","volume":"121","author":"T Wang","year":"2023","journal-title":"Int Immunopharmacol"},{"issue":"3","key":"pone.0313097.ref005","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s11882-009-0030-5","article-title":"The role of innate immunity in the pathogenesis of chronic rhinosinusitis","volume":"9","author":"AP Lane","year":"2009","journal-title":"Curr Allergy Asthma Rep"},{"issue":"3","key":"pone.0313097.ref006","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/s41423-020-00541-3","article-title":"Macrophages and the maintenance of homeostasis","volume":"18","author":"DM Mosser","year":"2021","journal-title":"Cellular & Molecular Immunology."},{"key":"pone.0313097.ref007","doi-asserted-by":"crossref","first-page":"1047930","DOI":"10.3389\/fimmu.2022.1047930","article-title":"M2 macrophage-related gene signature in chronic rhinosinusitis with nasal polyps","volume":"13","author":"Y Zhu","year":"2022","journal-title":"Front Immunol"},{"issue":"6","key":"pone.0313097.ref008","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41580-020-0237-9","article-title":"Guidelines and definitions for research on epithelial-mesenchymal transition","volume":"21","author":"J Yang","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"10","key":"pone.0313097.ref009","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1159\/000524950","article-title":"The Role of Epithelial-Mesenchymal Transition in Chronic Rhinosinusitis","volume":"183","author":"Y Xia","year":"2022","journal-title":"Int Arch Allergy Immunol"},{"issue":"2","key":"pone.0313097.ref010","doi-asserted-by":"crossref","first-page":"e1380765","DOI":"10.1080\/2162402X.2017.1380765","article-title":"Tumor-associated macrophages remodeling EMT and predicting survival in colorectal carcinoma.","volume":"7","author":"S Li","year":"2018","journal-title":"Oncoimmunology"},{"issue":"13","key":"pone.0313097.ref011","doi-asserted-by":"crossref","DOI":"10.3390\/ijms22136995","article-title":"Macrophage Polarization States in the Tumor Microenvironment.","volume":"22","author":"AJ Boutilier","year":"2021","journal-title":"Int J Mol Sci."},{"issue":"4","key":"pone.0313097.ref012","article-title":"Role of Nasal Fibroblasts in Airway Remodeling of Chronic Rhinosinusitis: The Modulating Functions Reexamined.","volume":"24","author":"JM Shin","year":"2023","journal-title":"Int J Mol Sci."},{"issue":"1","key":"pone.0313097.ref013","first-page":"39","article-title":"Evaluation of MMP-12 expression in chronic rhinosinusitis with nasal polyposis.","volume":"60","author":"S Lygeros","year":"2022","journal-title":"Rhinology"},{"issue":"6","key":"pone.0313097.ref014","article-title":"DNMTs Are Involved in TGF-\u03b21-Induced Epithelial-Mesenchymal Transitions in Airway Epithelial Cells.","volume":"23","author":"JH Park","year":"2022","journal-title":"Int J Mol Sci."},{"issue":"1","key":"pone.0313097.ref015","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41392-023-01452-1","article-title":"Macrophages in immunoregulation and therapeutics.","volume":"8","author":"S Chen","year":"2023","journal-title":"Signal Transduct Target Ther"},{"issue":"6","key":"pone.0313097.ref016","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19061801","article-title":"Role of Human Macrophage Polarization in Inflammation during Infectious Diseases.","volume":"19","author":"C Atri","year":"2018","journal-title":"Int J Mol Sci"},{"key":"pone.0313097.ref017","doi-asserted-by":"crossref","first-page":"e14053","DOI":"10.7717\/peerj.14053","article-title":"Macrophages play a key role in tissue repair and regeneration.","volume":"10","author":"Y Yu","year":"2022","journal-title":"PeerJ."},{"key":"pone.0313097.ref018","doi-asserted-by":"crossref","first-page":"678457","DOI":"10.3389\/fimmu.2021.678457","article-title":"Roles of Macrophage Polarization and Macrophage-Derived miRNAs in Pulmonary Fibrosis.","volume":"12","author":"A Kishore","year":"2021","journal-title":"Front Immunol."},{"issue":"2","key":"pone.0313097.ref019","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.yexcr.2019.03.018","article-title":"MMP-12 regulates proliferation of mouse macrophages via\u2002the ERK\/P38\u2002MAPK\u2002pathways during inflammation","volume":"378","author":"C Guan","year":"2019","journal-title":"Exp Cell Res"},{"issue":"1","key":"pone.0313097.ref020","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00418-017-1608-y","article-title":"Expression of matrix metalloproteinase 12 is highly specific for non-proliferating invasive trophoblasts in the first trimester and temporally regulated by oxygen-dependent mechanisms including HIF-1A","volume":"149","author":"U Hiden","year":"2018","journal-title":"Histochemistry and Cell Biology"},{"issue":"3","key":"pone.0313097.ref021","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1517\/14728220902751632","article-title":"Macrophage metalloelastase (MMP-12) as a target for inflammatory respiratory diseases.","volume":"13","author":"V Lagente","year":"2009","journal-title":"Expert Opin Ther Targets"},{"issue":"21","key":"pone.0313097.ref022","doi-asserted-by":"crossref","first-page":"12911","DOI":"10.1021\/acs.jmedchem.0c01285","article-title":"Therapeutic Targeting of MMP-12 for the Treatment of Chronic Obstructive Pulmonary Disease","volume":"63","author":"C Baggio","year":"2020","journal-title":"J Med Chem"},{"issue":"21","key":"pone.0313097.ref023","doi-asserted-by":"crossref","first-page":"438","DOI":"10.21037\/atm.2016.08.53","article-title":"THP-1 cells as a model for human monocytes.","volume":"4","author":"H Bosshart","year":"2016","journal-title":"Ann Transl Med"},{"key":"pone.0313097.ref024","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.diff.2022.10.001","article-title":"Macrophage polarization in THP-1 cell line and primary monocytes: A systematic review","volume":"128","author":"ZN Mohd Yasin","year":"2022","journal-title":"Differentiation"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0313097","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T18:29:06Z","timestamp":1735669746000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0313097"}},"subtitle":[],"editor":[{"given":"Zhiwen","family":"Luo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,12,31]]},"references-count":24,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0313097","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,31]]}}}