Matrix metalloproteinases in chronic rhinosinusitis

ABSTRACT

Introduction

Matrix metalloproteinases (MMPs) are a group of enzymes that are essential in maintaining extracellular matrix (ECM) homeostasis, regulating inflammation and tissue remodeling. In chronic rhinosinusitis (CRS), the overexpression of certain MMPs can contribute to chronic nasal tissue inflammation, ECM remodeling, and tissue repair.

Areas covered

This review provides a comprehensive overview of the biological characteristics and functions of the MMP family, particularly focusing on the expression and activity of MMPs in patients with CRS, and delves into their role in the pathogenesis of CRS and their potential as therapeutic targets.

Expert opinion

MMPs are important in tissue remodeling and have been implicated in the pathophysiology of CRS. Previous studies have shown that the expression of MMPs is upregulated in the nasal mucosa of patients with CRS and positively correlates with the severity of CRS. However, there is still a large gap in the research content of MMP in CRS, and the specific expression and pathogenic mechanism of MMP still need to be clarified. The significance and value of the ratio of MMP to tissue inhibitors of metalloproteinase (TIMP) in diseases still need to be demonstrated. Moreover, further studies are needed to assess the efficacy and safety of biologics that target MMPs in patients with CRS.

KEYWORDS:

• Chronic rhinosinusitis
• matrix metalloproteinase
• nasal polyps
• remodeling
• pathophysiology

Article highlights

• MMP family, such as MMP-1, −2, −3, −7, −8, and −9, present different expression levels in nasal mucosa of CRS with different endotypes. These MMPs may interact with the inflammatory environment, thus contributing to local mucosal tissue remodeling and disease progression.

• An imbalance in MMP and TIMP expression (which manifests as an increased MMP/TIMP ratio) may cause the abnormal local mucosal remodeling seen in CRSwNP.

• Evidence suggests that MMP-9 has potential value in predicting the therapeutic effect and prognosis of CRS.

Abbreviation

AERD, aspirin-exacerbated respiratory disease; Akt, protein kinase B; ALOX15, arachidonic acid-15-lipooxygenase; AP-1, activator protein-1; AR, allergic rhinitis; α-SMA, alpha-smooth muscle actin; BM, basement membrane; CIRP, Cold-induced RNA-binding protein; CRS, chronic rhinosinusitis; CRSsNP, chronic rhinosinusitis without nasal polyps; CRSwNP, chronic rhinosinusitis with nasal polyps; CXCL, chemoattractant CXC ligand; ECM, extracellular matrix; ECRS, eosinophilic chronic rhinosinusitis; ECRSwNP, eosinophilic chronic rhinosinusitis with nasal polyp; EDN, eosinophil-derived neurotoxin; EGFR, epidermal growth factor receptor; EMT, epithelial-mesenchymal transformation; ERK, extracellular signal-regulated kinases; FGF, fibroblast growth factor; GPI, glycosylphosphatidylinositol; IL, interleukin; JAK, Janus kinase; LAP, latency-associated peptide; LPS, lipopolysaccharide; LTBP, latent TGF-binding protein; MAPK, mitogen-activated protein kinases; MEK,mitogen-activated protein kinase kinase; MMP, matrix metalloproteinase; MT, membrane-type; NF-κB, nuclear factor kappa B; Raf, rapidly accelerated fibrosarcoma; SEMA4D, semaphorin 4D; STAT, signal transducers and activators of transcription; TAK, TGF-activated kinase; TGF, Transforming growth factor; TIMP, tissue inhibitors of metalloproteinase; TLR, Toll-like receptor; TNF-α, tumor necrosis factor-α; VEGF, vascular endothelial growth factor.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/1744666X.2024.2302362

Author contributions

Writing-Original Draft: Y Huang. Supervision: B Yan, C Meng. Writing-review & editing: L Zhang, C Wang.

Additional information

Funding

This work was supported by grants from National Natural Science Foundation of China [81900917, 82171108, 82025010, 81870698 and 82301329]; Changjiang Scholars and Innovative Research Team (IRT13082); CAMS Innovation Fund for Medical Sciences (2019-I2M-5-022); Beijing Municipal Science and Technology Project (Z181100001618002 and Z211100002921057); Capital’s Funds for Health Improvement and Research (CFH2022-1-1091); Beijing Municipal Administration of Hospitals’ Mission Plan (SML20150203); Beijing Municipal Administration of Hospitals’ Dengfeng plan (DFL20190202); Beijing Municipal Administration of Hospitals Incubating Program (PX2024010) Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes (JYY2023-1).