MicroRNA-21-5p promotes mucosal type 2 inflammation via regulating GLP1R/IL-33 signaling in chronic rhinosinusitis with nasal polyps.

Abstract

BACKGROUND:

It has been known that chronic rhinosinusitis with nasal polyps (CRSwNP) is a type 2 inflammation-dominated disease; however, the reasons causing such type of mucosal inflammation in CRSwNP are not well elucidated.

OBJECTIVE:

We sought to investigate the role of microRNA-21-5p (miR-21-5p) in regulating mucosal type 2 inflammation in CRSwNP.

METHODS:

miR-21-5p expression was detected in nasal mucosa of patients with CRSwNP. Correlations between miR-21-5p and indicators of type 2 inflammation were further analyzed. miR-21 knockout mice were used to explore the role of miR-21-5p in a murine model of eosinophilic (E) CRSwNP. Target gene of miR-21-5p related to type 2 inflammation in CRSwNP was identified.

RESULTS:

The upregulated miR-21-5p in the nasal mucosa of patients with CRSwNP, compared with control subjects, was expressed higher in patients with ECRSwNP than in patients with nonECRSwNP. miR-21-5p expression was positively correlated with mucosal eosinophil infiltrations and the expression of type 2 inflammatory cytokines. In the CRSwNP mice, miR-21 knockout significantly attenuated type 2 inflammation, as indicated by eosinophil infiltrations and expression of cytokines/chemokines in nasal mucosa and lavage fluid; moreover, genes associated with type 2 inflammation were extensively downregulated at the transcriptome level in miR-21 knockout mice. Glucagon-like peptide-1 receptor, which was negatively correlated with miR-21-5p expression in human nasal mucosa, was identified as the target of miR-21-5p. Overexpression of miR-21-5p induced IL-33 expression, whereas glucagon-like peptide-1 receptor agonist decreased IL-33 production in airway epithelial cells.

CONCLUSIONS:

miR-21-5p aggravates type 2 inflammation in the nasal mucosa of patients with CRSwNP via targeting glucagon-like peptide-1 receptor/IL-33 signaling, which may be a potential therapeutic target for CRSwNP.

• Authors: Ge Luan, Ming Wang, Jing Yuan, Xiangting Bu, Yang Wang, Sun Ying, Chengshuo Wang, Luo Zhang
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 150 Issue 6 Pg. 1460-1475 (12 2022) ISSN: 1097-6825 [Electronic] United States
• PMID: 35835254 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Interleukin-33
• Glucagon-Like Peptide-1 Receptor
• MicroRNAs
• MIRN21 microRNA, human
• MIRN21 microRNA, mouse

Topics

• Humans
• Mice
• Animals
• Nasal Polyps (genetics)
• Interleukin-33 (genetics)
• Glucagon-Like Peptide-1 Receptor
• Mice, Knockout
• MicroRNAs (genetics)