SCIENCE@home

DEP-induced ZEB2 promotes nasal polyp formation via epithelial-to-mesenchymal transition.

Mingyu Lee,Suha Lim,Yi-Sook Kim,Roza Khalmuratova,Seung‐Hyun Shin,Iljin Kim,Hyun-Jik Kim,Dong-Young Kim,C. Rhee,Jong-Wan Park,Hyun-Woo Shin

Published 2021 in Journal of Allergy and Clinical Immunology

ABSTRACT

BACKGROUND Diesel exhaust particles (DEP) 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 co-expression 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 or CRS patients 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 (HDM), followed by ZEB2 shRNA delivery. RESULTS Bioinformatics analyses revealed that DEP exposure triggered EMT features in airway epithelial cells (AECs). Similarly, DEP-exposed human nasal epithelial cells (hNECs) exhibited EMT characteristics, which were dependent on ZEB2 expression. hNEC-derived from chronic rhinosinusitis (CRS) patients presented more prominent EMT features after DEP treatment, when compared to those from control subjects and NP patients. Co-exposure to DEP and HDM 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.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-77 of 77 references · Page 1 of 1

CITED BY

Showing 1-38 of 38 citing papers · Page 1 of 1