RORA Overexpression Alleviates Nasal Mucosal Injury and Enhances Red Blood Cell Immune Adhesion Function in a Mouse Model of Allergic Rhinitis via Inactivation of the Wnt/β-Catenin Signaling Pathway

Background: In this study, we examined whether RORA (retinoic acid receptor-related orphan receptor alpha) was capable of alleviating the progression of allergic rhinitis (AR). Methods: In order to elucidate the possible effects of RORA and the regulatory mechanism between RORA and the Wnt/beta-catenin signaling pathway, mouse AR models were established and treated with RORA vector, siRNA against RORA, or the Wnt/beta-catenin pathway inhibitor WIF-1. Subsequently, the serum levels of inflammatory cytokines (IgE, INF-gamma, IL-1 beta, IL-4, and IL-17), red blood cell (RBC) immune adhesion function, the levels of RORA, beta-catenin, and GSK3 beta, as well as the extent of beta-catenin and GSK-3 beta phosphorylation were evaluated and measured. Results: The OVA-induced AR mouse model exhibited obvious nasal mucosal injury and inflammatory cell infiltration. RORA overexpression or the inactivation of the Wnt/beta-catenin signaling pathway was uncovered as a way to ameliorate nasal mucosal injury and eosinophil infiltration of the OVA-induced AR mouse model. On the other hand, it reduced the number of eosinophils and mast cells, which also resulted in downregulated expression of IgE, INF-gamma, IL-1 beta, IL-4, IL-17, beta-catenin, and GSK-3 beta. Moreover, this led to a decreased extent of beta-catenin and GSK-3 beta phosphorylation, while the rates of C(3)b receptor rosette and Ic rosette were elevated. Conclusion: Taken together, the key findings provided evidence suggesting that the elevated RORA could potentially alleviate nasal mucosal injury and simultaneously enhance RBC immune adhesion function through the inhibition of the Wnt/beta-catenin signaling pathway activation in an OVA-induced AR mouse model. This emphasizes a novel therapeutic target for the treatment of AR.