PM2.5 Induced Airway Remodeling via Wnt5a/β-catenin Pathway in Chronic Obstructive Pulmonary Diseases

Abstract Background: PM2.5-associated airway remodeling has recently been recognized as a central feature of COPD. The activation of Wnt/β-catenin pathway is closely related to the occurrence of airway remodeling. Accordingly, the goal of this study was to determine whether Wnt5a/β-Catenin is involved in PM2.5-induced smooth muscle proliferation in vivo and vitro, which promoted the development of airway remodeling in COPD.Methods: The effect of Wnt5a on β-Catenin-mediated airway remodeling was assessed by using an in vivo model of PM2.5-induced COPD and PM2.5-exposed human bronchial smooth muscle cell (HBSMC) in vitro. Small animal spirometry to measure lung function in mice. H&E staining and immunohistological inspection of emphysema and airway remodeling indexes. qPCR to detect Wnt5a, β-Catenin, TGF-β1, CyclinD1 and c-myc mRNA expression. CCK8 assay for cellular activity. Western blotting for PCNA, α-SMA, Wnt5a, β-Catenin, PDGFRβ and TenascinC protein expression. Detection of β-Catenin expression by cellular immunofluorescence.Results: The exposure to PM2.5 led to emphysema, airway wall thickening, increased smooth muscle layer thickness, decreased lung function and induced the expression of Wnt5a, β-Catenin, PDGFRβ and Tenascin C protein expression in lung tissue of mice. BOX5 alleviated PM2.5-induced these outcomes in mice. Moreover, PM2.5 induced the mRNA expression of Wnt5a, β-Catenin, TGF-β1, CyclinD1 and c-myc in HBSMC. BOX5 also inhibited PM2.5-induced the increase of PCNA, α-SMA, Wnt5a, β-Catenin, PDGFRβ and Tenascin C protein expression in HBSMC. Conclusions: Our findings suggest that PM2.5 exposure induce HBSMC proliferation, contributing to airway remodeling via Wnt5a/β-Catenin signaling pathway in vivo and in vitro, which could be a target of treatment of COPD.