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Wnt pathway in pulmonary fibrosis in the bleomycin mouse model.

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1
Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.

Abstract

BACKGROUND:

The Wnt/beta-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-beta in conjunction with the Wnt/beta-catenin signaling pathway. LacZ expression reveals the Wnt/beta-catenin signaling pathway through the activated (nuclear) beta-catenin and coactivation of LEF/TCF transcription factors. X-gal staining and immunohistochemical staining of beta-catenin, cyclin D1, MMP-7, and TGF-beta 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 beta-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-beta was faintly staining in alveolar macrophages and epithelial cells at 3 weeks.

CONCLUSION:

The Wnt/beta-catenin pathway is activated in bleomycin-induced lung fibrosis, and downstream genes were localized in AM, alveolar epithelium, and interstitium.

PMID:
19817697
PMCID:
PMC3704199
[Indexed for MEDLINE]
Free PMC Article
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