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Journal of Environmental Pathology, Toxicology and Oncology
Fator do impacto: 1.241 FI de cinco anos: 1.349 SJR: 0.356 SNIP: 0.613 CiteScore™: 1.61

ISSN Imprimir: 0731-8898
ISSN On-line: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.v28.i2.20
pages 99-108

Wnt Pathway in Pulmonary Fibrosis in the Bleomycin Mouse Model

Li Liu
Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, 550 1st Ave, New York, NY 10016
Benjamin Carron
Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, 550 1st Ave, New York, NY 10016
Herman T. Yee
Departments of Pathology and Environmental Medicine, and Division of Pulmonary and Critical Care Medicine. NYU School of Medicine, New York, NY 10016
Ting-An Yie
Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
Mustapha Hajjou
Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA
William N. Rom
Division of Pulmonary and Critical Care Medicine, and Department of Environmental Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA

RESUMO

Background: The Wnt/β-catenin signaling pathway plays an important role in regulating cellular differentiation, proliferation, and polarity. Methods: We used bleomycin to induce lung fibrosis in a transgenic Wnt reporter mouse to characterize the expression pattern of cyclin D1, MMP-7, and TGF-β in conjunction with the Wnt/β-catenin signaling pathway. LacZ expression reveals the Wnt/β-catenin signaling pathway through the activated (nuclear) β-catenin and coactivation of LEF/TCF transcription factors. X-gal staining and immunohistochemical staining of β-catenin, cyclin D1, MMP-7, and TGF-β were assessed after bleomycin administration. Results: We observed LacZ expression in bronchiolar proliferative lesions and the epithelium in remodeled cystic and fibrotic areas at both 1 and 3 weeks. Nuclear β-catenin staining was prominent in epithelial cells of remodeled and fibrotic areas at 3 weeks. MMP-7 was faint in basement membranes of airways and matrix zones in fibrotic areas at 3 weeks. Cyclin D1 was observed in alveolar macrophages (AM), alveolar epithelium, and fibrotic areas consistent with rapid cell turnover in these areas at both 1 and 3 weeks. TGF-β was faintly staining in alveolar macrophages and epithelial cells at 3 weeks. Conclusion: The Wnt/β-catenin pathway is activated in bleomycin-induced lung fibrosis, and downstream genes were localized in AM, alveolar epithelium, and interstitium.