Expression Profiles of Matrix Metalloproteinases and Their Inhibitors in Nasal Polyps

Chen Duan; Xuemin Yu; Xin Feng; Li Shi; Deyun Wang

doi:10.2147/JIR.S438581

Expression Profiles of Matrix Metalloproteinases and Their Inhibitors in Nasal Polyps

J Inflamm Res. 2024 Jan 3:17:29-39. doi: 10.2147/JIR.S438581. eCollection 2024.

Authors

Chen Duan¹, Xuemin Yu², Xin Feng¹, Li Shi³, Deyun Wang⁴

Affiliations

¹ Department of Otorhinolaryngology, Qilu Hospital of Shandong University, National Health Commission (NHC) Key Laboratory of Otorhinolaryngology, Shandong University, Jinan, Shandong, 250000, People's Republic of China.
² Department of Otorhinolaryngology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, NHC Key Laboratory of Otorhinolaryngology (Shandong University), Qingdao, Shandong, 250000, People's Republic of China.
³ Department of Otolaryngology, The Second Hospital of Shandong University, Jinan, Shandong, 250000, People's Republic of China.
⁴ Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Abstract

Purpose: Nasal polyp (NP) is characterized by inflammation of the sinonasal mucosa with predominant inflammatory cell infiltration. Matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) are recognized to play an important role in leukocyte migration in airway inflammation. Herein, efforts were made to confirm the expression levels of MMPs/TIMPs and study the relationship between the infiltration of inflammatory cells and local expression levels of MMPs/TIMPs in NPs.

Patients and methods: NP tissues were obtained from 42 Chinese patients with bilateral nasal polyps during the endoscopic sinus surgery. Inferior turbinate (IT) tissues from 19 patients with septal deviation were taken during the rhinoplasty surgery as controls. mRNA and protein levels of MMP1, MMP9, MMP10, MMP12, TIMP1 and TIMP3 were assessed by quantitative PCR and immunohistochemistry.

Results: Eosinophilia (72%, 23/32 samples), neutrophilia (41%, 13/32 samples), and increase in macrophages (38%, 12/32 samples) were found in NP tissues. mRNA expression of MMP1 (10.9-fold), MMP9 (4.1-fold), MMP10 (6.7-fold) and MMP12 (3.5-fold) were significantly up-regulated, while TIMP1 (1.5-fold) and TIMP3 (6.0-fold) were significantly down-regulated in NPs (n=42) as compared to the controls (n=19). The immunostaining levels of all 4 MMPs and two TIMPs were higher in NPs than those in controls. The co-localization of MMP1/MMP10/MMP12 and macrophages were identified in NPs. MMP9 was mainly expressed in neutrophils, while TIMP1 or TIMP3 were mostly found in eosinophils in NPs.

Conclusion: The results of our study indicate that tissue remodeling is significant in NPs, where MMPs/TIMPs play important roles in both tissue remodeling and inflammatory cells infiltration.

Keywords: extracellular matrix; inflammatory cells; matrix metalloproteinases; remodeling.

Grants and funding

This study is supported by Shandong Natural Science Foundation (ZR2020QH151), the National Natural Science Foundation of China (82171106 and 81700890), and Taishan Scholar Program of Shandong Province (tsqn202103166).