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Published on: August 25, 2017
PM2.5 Induces Airway Remodeling in Chronic Obstructive Pulmonary Diseases via the Wnt5a/β-Catenin Pathway
Weifeng Zou1, Xiaoqian Wang2, Ruiting Sun3
1State Key Laboratory of Respiratory Disease, Guangzhou Chest Hospital, Guangzhou, Guangdong, People's Republic of China.
Background:
Fine-particulate matter ≤2.5 μm in diameter (PM2.5)-associated airway remodeling has recently been recognized as a central feature of COPD. Activation of the Wnt/β-catenin pathway is closely related to the occurrence of airway remodeling. Accordingly, the goal of this study was to determine whether the Wnt5a/β-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 β-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, β-Catenin, TGF-β1, CyclinD1 and c-myc mRNA expression. The CCK8 assay was performed to detect cellular activity. Western blotting was performed to assess PCNA, α-SMA, Wnt5a, β-Catenin, PDGFRβ and TenascinC protein expression. β-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, β-Catenin, PDGFRβ 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, β-Catenin, TGF-β1, CyclinD1 and c-myc mRNAs in HBSMCs. BOX5 also inhibited the PM2.5-induced increases in PCNA, α-SMA, Wnt5a, β-Catenin, PDGFRβ 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/β-Catenin signaling pathway in vivo and in vitro, which might be a target for COPD treatment.
Insights
Fine particulate matter (PM2.5) exposure triggers airway remodeling in COPD by activating the Wnt5a/β-Catenin pathway. This pathway promotes smooth muscle proliferation, suggesting it as a potential therapeutic target for COPD treatment.
Area of Science:
- Pulmonary Medicine
- Cellular Biology
- Environmental Health
Background:
- Airway remodeling is a key feature of Chronic Obstructive Pulmonary Disease (COPD).
- PM2.5 exposure is increasingly linked to airway remodeling.
- The Wnt/β-catenin pathway plays a role in airway remodeling.
Purpose of the Study:
- To investigate the role of the Wnt5a/β-Catenin pathway in PM2.5-induced airway remodeling.
- To determine if PM2.5 induces smooth muscle proliferation via this pathway in COPD models.
Main Methods:
- Utilized an in vivo mouse model of PM2.5-induced COPD and in vitro human bronchial smooth muscle cells (HBSMCs).
- Assessed lung function, histological changes, and gene/protein expression (Wnt5a, β-Catenin, proliferation markers).
- Employed spirometry, H&E staining, immunohistochemistry, RT-PCR, CCK8 assay, and Western blotting.
Main Results:
- PM2.5 exposure caused emphysema, airway thickening, and increased smooth muscle layer in mice, which were ameliorated by a Wnt5a antagonist (BOX5).
- PM2.5 exposure increased Wnt5a, β-Catenin, and proliferation markers in HBSMCs.
- BOX5 inhibited PM2.5-induced proliferation and Wnt5a/β-Catenin pathway activation in HBSMCs.
Conclusions:
- PM2.5 exposure drives HBSMC proliferation and airway remodeling through the Wnt5a/β-Catenin pathway.
- This pathway represents a potential therapeutic target for managing PM2.5-associated COPD.
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