PM2.5 Induces Airway Remodeling in Chronic Obstructive Pulmonary Diseases via the Wnt5a/ß-Catenin Pathway.
Int J Chron Obstruct Pulmon Dis
; 16: 3285-3295, 2021.
Article
in En
| MEDLINE
| ID: mdl-34887658
ABSTRACT
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/ß-catenin pathway is closely related to the occurrence of airway remodeling. Accordingly, the goal of this study was to determine whether the Wnt5a/ß-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 ß-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, ß-Catenin, TGF-ß1, 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, ß-Catenin, PDGFRß and TenascinC protein expression. ß-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, ß-Catenin, PDGFRß 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, ß-Catenin, TGF-ß1, CyclinD1 and c-myc mRNAs in HBSMCs. BOX5 also inhibited the PM2.5-induced increases in PCNA, α-SMA, Wnt5a, ß-Catenin, PDGFRß 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/ß-Catenin signaling pathway in vivo and in vitro, which might be a target for COPD treatment.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pulmonary Disease, Chronic Obstructive
/
Airway Remodeling
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Int J Chron Obstruct Pulmon Dis
Year:
2021
Document type:
Article