The Role Of MicroRNA-218-5p In Airway Inflammation In Asthma

Background: Micro RNA(miR)-218-5p is involved in cigarette smoke-induced airway inflammation.In our earlier asthma epithelial miRNA profiling data,miR-218-5p was the top 2 downregulated miRNA.We hypothesize that miR-218-5p plays a role in asthma airway inflammation.Objective: To unveil the role of miR-218-5p and its target gene in asthma airway inflammation.Methods: We measured miR-218-5p expression in bronchial brushings of asthmatic patients(n=50)and healthy controls(n=15),and analyzed the correlations between miR-218-5p expression and airway eosinophilia.We examined whether CTNND2 was a target of miR-218-5p,and the expression of 12 catenin family members in bronchial brushings and cultured human bronchial epithelial(HBE)cells.We explored the role of miR-218-5p-CTNND2 pathway using a murine model of allergic airway inflammation.Results: Epithelial miR-218-5p expression was significantly decreased and negatively correlated with eosinophils in induced sputum and bronchial biopsies,and other type 2 biomarkers in asthmatic patients.We verified that CTNND2(encoding ?-catenin)was a target of miR-218-5p.Remarkably,CTNND2 was the most significantly upregulated catenin compared to the other 11 catenin family members in bronchial brushings of asthmatic patients and IL-13-stimulated HBE cells.Moreover,epithelial CTNND2 expression positively correlated with airway eosinophilia in asthma.Airway miR-218-5p expression was also decreased and Ctnnd2 expression was increased in a murine model of allergic airway inflammation.Intriguingly,miR-218-5p overexpression suppressed airway hyperresponsiveness,eosinophilic airway inflammation and Ctnnd2 upregulation in the mouse model.Finally,perturbation of miR-218-5p or CTNND2 expression significantly altered chemokine CCL26 expression in the cell cultures and the mouse model.Conclusions & Clinical Relevance: Epithelial miR-218-5p plays a protective role in eosinophilic airway inflammation via targeting CTNND2,a novel catenin in asthma,and suppressing chemokine CCL26 expression.