MUC13 enhances IL-17 signaling pathway activity in nasal epithelial cells.

Background

MUC13 is a membrane-bound mucin involved in epithelial protection and barrier maintenance, but its role in nasal epithelial inflammation remains unclear. This study aimed to investigate whether MUC13 regulates inflammatory signaling in primary nasal epithelial cells (NECs).

Methods

Patient-derived primary NECs were transfected with human MUC13 mRNA to establish a dose-dependent overexpression model, and RNA sequencing was performed to characterize MUC13-associated transcriptomic changes. Differential expression analysis, GO/KEGG enrichment analysis, and GSEA were used to identify altered biological pathways, followed by qRT-PCR and ELISA validation of selected inflammatory mediators.

Results

MUC13 overexpression induced dose-dependent global transcriptomic changes and significantly enriched multiple immune recognition- and inflammation-related pathways, among which the IL-17 signaling pathway showed consistent positive enrichment. Functional validation further showed that MUC13 overexpression increased the expression of IL-17-related downstream genes, including CXCL6, CXCL8, CSF3, CCL20, LCN2, and MMP9, and enhanced the secretion of G-CSF, CXCL8, and LCN2. Pharmacological inhibition of NF-κB attenuated these MUC13-induced inflammatory responses, suggesting that NF-κB signaling may, at least in part, mediate MUC13-associated IL-17-related responses. Analyses of public transcriptomic data and clinical nasal mucosal samples further supported a positive association between MUC13 expression and IL-17 signaling activity in nasal mucosal tissues.

Conclusion

Collectively, these findings identify MUC13 as an active regulator of nasal epithelial inflammatory responses and suggest that MUC13 promotes IL-17-associated downstream responses, potentially through NF-κB signaling.