J Rhinol.  2024 Jul;31(2):67-77. 10.18787/jr.2024.00022.

Epithelial-Mesenchymal Transition in Chronic Rhinosinusitis

• Choi T
• Ryu S
• Bae JS
• Yoo SH
• Mo JH

• KMID: 2558232
• DOI: http://doi.org/10.18787/jr.2024.00022

Abstract

Chronic rhinosinusitis (CRS) is characterized by prolonged inflammation of the nasal and paranasal sinus mucosa lasting over 12 weeks. CRS is divided into two main types based on the presence of nasal polyps: CRS without nasal polyps and CRS with nasal polyps. The condition is further classified into endotypes based on type 1, type 2, and type 3 inflammatory signatures, with differences in terms of disease severity, prognosis, and treatment response. Recent studies have emphasized the importance of the epithelial-mesenchymal transition (EMT) in CRS progression. In CRS, the EMT can be triggered by infections, allergens, hypoxia, and environmental pollutants. Specifically, EMT induction proceeds through the following mechanisms: viral and bacterial infections disrupt the epithelial barrier, house dust mites and other allergens activate the TGF-β and EGFR signaling pathways, hypoxia increases HIF-1α and other mesenchymal markers, and diesel exhaust particles and particulate matter cause oxidative stress. Maintaining the integrity of the epithelial barrier is essential for nasal mucosa homeostasis. In CRS, barrier damage activates repair processes that trigger the EMT, resulting in barrier dysfunction and tissue remodeling. Epithelial barrier dysfunction allows antigens and pathogens to penetrate, perpetuating inflammation and promoting the EMT. This disruption is a hallmark of CRS, emphasizing the importance of barrier integrity in the development of the disease. Key signaling pathways regulating the EMT in CRS include TGF-β, Wnt, HMGB1, AGE/ERK, TNF-α, and various miRNAs. These signaling pathways connect to various downstream pathways, such as the Smad2/3, GSK-3β/β-catenin, RAGE, and NF-κB pathways. This review focuses on the complex mechanisms of the EMT in CRS, emphasizing the role of epithelial barrier dysfunction and subsequent EMT processes in driving the disease’s development and progression. A deeper understanding of these EMT-driven mechanisms will help identify the potential therapeutic targets aimed at restoring epithelial integrity and reversing the EMT.

Keyword

Chronic rhinosinusitis; Epithelial-mesenchymal transition; Nasal mucosa; Airway remodeling

Figure

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  Fig. 1. Mechanisms and risk factors of the epithelial-mesenchymal transition in chronic rhinosinusitis. DEP, diesel exhaust particle; PM, particulate matter; HDM, home dust mite; SPINK5, serine peptidase inhibitor Kazal type 5; HIF-1α, hypoxia inducible factor-1α; BMP2, bone morphogenetic protein 2; ECM, extracellular matrix; ZO-1, zonula occludens-1; α-SMA, α-smooth muscle actin; EMT-TFs, EMT transcription factors.

• 

  Fig. 2. Intracellular signaling of the epithelial-mesenchymal transition process studied in chronic rhinosinusitis. TGF-β, transforming growth factor beta; EGF, epidermal growth factor; AGEs, advanced glycation end-products; RAGE, receptor for advanced glycation end-products; HMGB1, high mobility group box 1; Wnt, wingless/integrase-1; TNF-α, tumor necrosis factor-alpha; ERK, extracellular signal regulated kinase; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; HIF-1α, hypoxia inducible factor-1α; EMT-TFs, EMT transcription factors.

Reference

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