Epithelial cell dysfunction in chronic rhinosinusitis: the epithelial–mesenchymal transition

ABSTRACT

Introduction

Epithelial–mesenchymal transition (EMT) is a type of epithelial cell dysfunction, which is widely present in the nasal mucosa of patients with chronic rhinosinusitis (CRS), especially CRS with nasal polyps, and contributes to pathogenesis of the disease. EMT is mediated via complex mechanisms associated with multiple signaling pathways.

Areas covered

We have summarized the underlying mechanisms and signaling pathways promoting EMT in CRS. Strategies or drugs/agents targeting the genes and pathways related to the regulation of EMT are also discussed for their potential use in the treatment of CRS and asthma. A literature search of studies published in English from 2000 to 2023 was conducted using the PubMed database, employing CRS, EMT, signaling, mechanisms, targeting agents/drugs, as individual or combinations of search terms.

Expert opinion

EMT in nasal epithelium not only leads to epithelial cell dysfunction but also plays an important role in nasal tissue remodeling in CRS. A comprehensive understanding of the mechanisms underlying EMT and the development of drugs/agents targeting these mechanisms may provide new treatment strategies for CRS.

KEYWORDS:

• Chronic rhinosinusitis
• epithelial cell dysfunction
• epithelial–mesenchymal transition
• EMT-targeting agents/drugs
• microRNAs
• Mitogen-activated protein kinase
• transforming growth factor-β

Article highlights

• Chronic rhinosinusitis (CRS) is a chronic inflammation of the nasal mucosa accompanied by extensive epithelial cell dysfunction.

• Epithelial–mesenchymal transition (EMT) occurs widely in the nasal epithelium and polyps of CRS patients and is promoted via TGF-β, Wnt, HIF-1α, and MAPK signaling pathways, as well as microRNAs.

• Drugs/agents targeting the key components of mechanisms and pathways associated with EMT have been shown to inhibit or reverse EMT in CRS and asthma.

• Most of the drugs/agents targeting EMT are at the experimental stage and need to be investigated further before they can be tested further in preclinical trials for safety and efficacy in clinical use for the treatment of CRS in the long term.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by grants from national key R&D program of China (2022YFC2504100), national natural science foundation of China (82025010, 82171109), the program for the Changjiang scholars and innovative research team (IRT13082), Beijing municipal administration of hospitals’ Dengfeng/Youth plan (DFL20190202, QML20200202), and CAMS Innovation Fund for Medical Sciences (2019-I2M-5-022).