MicroRNA-23a contributes to asthma by targeting BCL2 in airway epithelial cells and CXCL12 in fibroblasts.

Abstract

The deregulated cross-talk between airway epithelial cells with subepithelial fibroblasts during inflammation drives the pathogenesis of asthma. Bioinformatics analysis and luciferase activity assay suggested that B cell lymphoma-2 (BCL2) and CXC ligand 12 (CXCL12) are potential targets of miR-23a. The aim of this study was to elucidate the effect of microRNA-23a (miR-23a) on BCL2, and CXCL12 in asthma. In E3 rats, miR-23a was upregulated in lung tissues after antigen-induced pulmonary inflammation during acute and chronic inflammation. Immunohistochemistry showed downregulation of BCL2 in the epithelium and of CXCL12 in subepithelial fibroblasts and smooth muscle cells. Treatment of isolated cells with miR-23a mimic or inhibitor modified the expression of BCL2 and of CXCL12 in the expected cell type-specific manner. Moreover, in epithelial cells, interleukin-4 upregulated miR-23a expression and thereby decreased the expression of BCL2, while increasing the caspase-3 expression, which was followed by apoptosis. In fibroblasts, the expression of miR-23a was increased by thymic stromal lymphopoietin (TSLP). Consequently, the CXCL12 expression was abrogated. The phosphorylation of CREB was also downregulated by TSLP through the action of miR-23a. This study describes a novel mechanism, where miR-23a is an important cell type-specific regulator for asthma-associated airway wall remodeling parameter. Thus, miR-23a may present a potential new target for the therapy of asthma.