PM2.5 Induces Airway Remodeling in Chronic Obstructive Pulmonary Diseases via the Wnt5a/beta-Catenin Pathway

Background: Fine-particulate matter <= 2.5 mu m in diameter (PM2.5)-associated airway remodeling has recently been recognized as a central feature of COPD. Activation of the Wnt/beta-catenin pathway is closely related to the occurrence of airway remodeling. Accordingly, the goal of this study was to determine whether the Wnt5a/beta-Catenin pathway is involved in PM2.5-induced smooth muscle proliferation in vivo and in vitro, which promotes the development of airway remodeling in subjects with COPD. Methods: The effect of Wnt5a on beta-Catenin-mediated airway remodeling was assessed using an in vivo model of PM2.5-induced COPD and PM2.5-exposed human bronchial smooth muscle cells (HBSMCs) in vitro. Small animal spirometry was used to measure lung function in mice. H&E staining and immunohistochemistry were performed to inspect emphysema and airway remodeling indices. Real-time PCR was used to detect Wnt5a, beta-Catenin, TGF-beta 1, CyclinD1 and c-myc mRNA expression. The CCK8 assay was performed to detect cellular activity. Western blotting was performed to assess PCNA, alpha-SMA, Wnt5a, beta-Catenin, PDGFR beta and TenascinC protein expression. beta-Catenin expression was detected using cellular immunofluorescence. Results: Exposure to PM2.5 led to emphysema, airway wall thickening, an increased smooth muscle layer thickness, decreased lung function and increased expression of the Wnt5a, beta-Catenin, PDGFR beta and Tenascin C proteins in the mouse lung tissue. BOX5 (a Wnt5a antagonist) alleviated these PM2.5-induced outcomes in mice. Moreover, PM2.5 induced the expression of the Wnt5a, beta Catenin, TGF-beta 1, CyclinD1 and c-myc mRNAs in HBSMCs. BOX5 also inhibited the PM2.5-induced increases in PCNA, alpha-SMA, Wnt5a, beta-Catenin, PDGFR beta and Tenascin C protein expression in HBSMCs. Conclusion: Our findings suggest that PM2.5 exposure induces HBSMC proliferation, contributing to airway remodeling via the Wnt5a/beta-Catenin signaling pathway in vivo and in vitro, which might be a target for COPD treatment.