CHI3L1 on fibrinolytic system imbalance in chronic rhinosinusitis with nasal polyp.

Autor:	Yang HW; Upper Airway Chronic Inflammatory Diseases Laboratory, Korea University College of Medicine, Seoul, Republic of Korea., Park JH; Upper Airway Chronic Inflammatory Diseases Laboratory, Korea University College of Medicine, Seoul, Republic of Korea., Shin JM; Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Anam Hospital, Seoul, Republic of Korea., Son HG; Upper Airway Chronic Inflammatory Diseases Laboratory, Korea University College of Medicine, Seoul, Republic of Korea.; Medical Device Usability Test Center, Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea., Kim TH; Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Anam Hospital, Seoul, Republic of Korea., Lee SH; Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Ansan Hospital, Ansan, Republic of Korea., Park IH; Upper Airway Chronic Inflammatory Diseases Laboratory, Korea University College of Medicine, Seoul, Republic of Korea.; Medical Device Usability Test Center, Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea.; Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Guro Hospital, Seoul, Republic of Korea.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Jun 21; Vol. 15, pp. 1410948. Date of Electronic Publication: 2024 Jun 21 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1410948
Abstrakt:	Background: Chronic rhinosinusitis (CRS) is an inflammatory disease affecting more than 10% of the global adult population. It is classified into Th1, Th2, and Th17 endotypes and eosinophilic and non-eosinophilic types. Th2-based inflammation and eosinophilic CRS (ECRS) are associated with tissue remodeling and fibrinolytic system impairment. Objective: To elucidate the role of eosinophils in inducing fibrin deposition in CRS nasal polyp tissues and explore potential regulatory mechanisms. Methods: We analyzed the expression of genes related to the serpin family and fibrinolytic system using Gene Expression Omnibus and Next-generation sequencing data. Differentially expression genes (DEGs) analysis was used to compare control and nasal polyp tissues, followed by KEGG and Gene ontology (GO) analysis. We measured the expression and correlation of plasminogen activator-1 (PAI-1), tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), and urokinase plasminogen activator surface receptor (u-PAR) in CRS tissues, and evaluated the effect of eosinophils on the fibrinolytic system using a cytokine array and co-culture. Results: Nasal polyp tissues showed upregulated PAI-1, u-PA, and u-PAR expression and downregulated t-PA expression. Fibrinolytic system-related genes positively correlated with Th2 cytokines, except for t-PA. Eosinophil-derived Chitinase-3-like protein 1 (CHI3L1) increased PAI-1 expression and decreased t-PA levels in fibroblasts and epithelial cells. The inhibition of CHI3L1 suppresses these alterations. Conclusion: CHI3L1 contributes to fibrin deposition by impairing the fibrinolytic system during nasal polyp formation. The regulation of CHI3L1 expression may inhibit fibrin deposition and edema in ECRS, presenting a potential treatment for this condition. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Yang, Park, Shin, Son, Kim, Lee and Park.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu