Wnt pathway in pulmonary fibrosis in the bleomycin mouse model.
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.


CONCLUSIONS
The Wnt/beta-catenin pathway is activated in bleomycin-induced lung fibrosis, and downstream genes were localized in AM, alveolar epithelium, and interstitium.
Liu
Li
L
Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University School of Medicine, New York, NY 10016, USA.
Carron
Benjamin
B
Yee
Herman T
HT
Yie
Ting-An
TA
Hajjou
Mustapha
M
Rom
William
W
D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D016676:Macrophages, Alveolar / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011658:Pulmonary Fibrosis / Q000139:chemically induced*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D051153:Wnt Proteins; D051176:beta Catenin; D001761:Bleomycin