Wnt/β-catenin signaling pathway regulates asthma airway remodeling by influencing the expression of c-Myc and cyclin D1 via the p38 MAPK-dependent pathway.

Abstract

Airway remodeling is the main characteristic of asthma; however, the mechanisms underlying this pathophysiological change have not been fully elucidated. Previous studies have indicated that the Wnt/β-catenin and mitogen-activated protein kinase (MAPK) signaling pathway are involved in the development of airway remodeling during asthma. Therefore, the present study established an airway remodeling rat model, after which β-catenin, cyclin D1 and c-Myc protein expressions were analyzed via western blotting in the lung tissue and airway smooth muscle cells (ASMCs) of rats. The mRNA expression of the aforementioned proteins were evaluated via reverse transcription-quantitative PCR. β-catenin, cyclin D1 and c-Myc are core transcription factors and target genes of the Wnt/β-catenin and MAPK signaling pathways. Furthermore, β-catenin, c-Myc and cyclin D1 protein expression were determined following blocking of the p38 MAPK signaling pathway in vitro. The results demonstrated that higher expressions of β-catenin, cyclin D1 and c-Myc were detected in lung tissues and ASMCs in the asthma group compared with the control. Blocking the p38 MAPK signaling pathway with a specific inhibitor SB203580 also downregulated the expressions of β-catenin, cyclin D1 and c-Myc in vitro. Taken together, these results indicated that the Wnt/β-catenin signaling pathway may regulate the process of airway remodeling via the p38 MAPK-dependent pathway.