S aureus upregulation of MUC13 modulates mucosal remodeling in chronic rhinosinusitis via MEK1/2 and WNT2B.

Abstract

Chronic rhinosinusitis (CRS)-related mucins affect nasal mucosal inflammation and pathological progression. MUC13 is expressed in various epithelial tissues and plays a role in inflammation, apoptosis, and infection, but its involvement in CRS remains unexplored. We sought to clarify the role of transmembrane-type MUC13 in CRS and analyze its modulatory function in pathological processes. MUC13 expression was evaluated in pathological tissues from patients with CRS and human nasal epithelial cells (HNECs) stimulated with Staphylococcus aureus exoproteins. IL6 secretion, lactate dehydrogenase release, and wound scratching in HNECs were detected after transfection with MUC13 overexpression vectors or small interfering RNA. Mitogen-activated protein kinase/extracellular signal-regulated kinase kinases 1/2 (MEK1/2, encoded by MAP2K1/2) phosphorylation and protein docking analyses were performed to explore the potential interactions between MUC13 and WNT2B. Muc13^-/- and wild-type mice were used to establish the CRS model, and cytokine levels and nasal mucosal pathology were evaluated in CRS mice. MUC13 was mainly expressed in nasal epithelial cells. S aureus exoproteins promote the MUC13 expression in HNECs. MUC13 expression was positively correlated with the migration of HNECs in the scratch-wound assay and negatively correlated with IL6 and lactate dehydrogenase secretion. MUC13 increased MEK1/2 phosphorylation and WNT2B expression. In CRS mice, Muc13 knockout increased IL6 and collagen expression, along with decreased WNT2B expression and mucosal thickness in the nasal mucosa. S aureus exoproteins increase MUC13 overexpression in HNECs in CRS. MUC13 promotes HNECs' repair in scratch-wound HNECs through MEK1/2 phosphorylation and WNT2B signaling. The Muc13^-/- CRS mouse model confirmed that the MUC13-WNT2B pathway is involved in CRS nasal mucosal inflammation, collagen deposition, and remodeling.