DEP-induced ZEB2 promotes nasal polyp formation via epithelial-to-mesenchymal transition - 05/01/22
Abstract |
Background |
Diesel exhaust particles (DEPs) are associated with the prevalence and exacerbation of allergic respiratory diseases, including allergic rhinitis and allergic asthma. However, DEP-induced mechanistic pathways promoting upper airway disease and their clinical implications remain unclear.
Objective |
We sought to investigate the mechanisms by which DEP exposure contributes to nasal polyposis using human-derived epithelial cells and a murine nasal polyp (NP) model.
Methods |
Gene set enrichment and weighted gene coexpression network analyses were performed. Cytotoxicity, epithelial-to-mesenchymal transition (EMT) markers, and nasal polyposis were assessed. Effects of DEP exposure on EMT were determined using epithelial cells from normal people or patients with chronic rhinosinusitis with or without NPs. BALB/c mice were exposed to DEP through either a nose-only exposure system or nasal instillation, with or without house dust mite, followed by zinc finger E-box-binding homeobox (ZEB)2 small hairpin RNA delivery.
Results |
Bioinformatics analyses revealed that DEP exposure triggered EMT features in airway epithelial cells. Similarly, DEP-exposed human nasal epithelial cells exhibited EMT characteristics, which were dependent on ZEB2 expression. Human nasal epithelial cells derived from patients with chronic rhinosinusitis presented more prominent EMT features after DEP treatment, when compared with those from control subjects and patients with NPs. Coexposure to DEP and house dust mite synergistically increased the number of NPs, epithelial disruptions, and ZEB2 expression. Most importantly, ZEB2 inhibition prevented DEP-induced EMT, thereby alleviating NP formation in mice.
Conclusions |
Our data show that DEP facilitated NP formation, possibly via the promotion of ZEB2-induced EMT. ZEB2 may be a therapeutic target for DEP-induced epithelial damage and related airway diseases, including NPs.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Diesel exhaust particles, air pollutants, nasal polyps, epithelial-to-mesenchymal transition, ZEB2
Abbreviations used : AEC, AR, ALI, BEGM, CRS, CRSsNP, CRSwNP, DEP, DMEM, DMSO, EMT, FITC, GI, GO, GSEA, HBEC, hNEC, HDM, PBST, PM, PM2.5, PM10, siRNA, SRM, TEER, WGCNA, ZEB
Plan
| This research was supported by the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, the Ministry of Health & Welfare, Republic of Korea (grant no. HI17C1669), and the National Research Foundation of Korea (grant no. 2020R1A4A2002903). |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. |
Vol 149 - N° 1
P. 340-357 - janvier 2022 Retour au numéro
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