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博来霉素小鼠模型中肺纤维化的Wnt信号通路

Wnt pathway in pulmonary fibrosis in the bleomycin mouse model.

作者信息

Liu Li, Carron Benjamin, Yee Herman T, Yie Ting-An, Hajjou Mustapha, Rom William

机构信息

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

出版信息

J Environ Pathol Toxicol Oncol. 2009;28(2):99-108. doi: 10.1615/jenvironpatholtoxicoloncol.v28.i2.20.

DOI:10.1615/jenvironpatholtoxicoloncol.v28.i2.20
PMID:19817697
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3704199/
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.

摘要

背景

Wnt/β-连环蛋白信号通路在调节细胞分化、增殖和极性方面发挥着重要作用。

方法

我们使用博来霉素在转基因Wnt报告小鼠中诱导肺纤维化，以结合Wnt/β-连环蛋白信号通路来表征细胞周期蛋白D1、基质金属蛋白酶-7（MMP-7）和转化生长因子-β（TGF-β）的表达模式。LacZ表达通过活化的（核）β-连环蛋白和LEF/TCF转录因子的共激活来揭示Wnt/β-连环蛋白信号通路。在给予博来霉素后，评估β-连环蛋白、细胞周期蛋白D1、MMP-7和TGF-β的X-gal染色和免疫组织化学染色。

结果

在第1周和第3周时，我们在细支气管增殖性病变以及重塑的囊性和纤维化区域的上皮中观察到LacZ表达。在第3周时，核β-连环蛋白染色在重塑和纤维化区域的上皮细胞中很明显。在第3周时，MMP-7在气道基底膜和纤维化区域的基质区中很微弱。在第1周和第3周时，在肺泡巨噬细胞（AM）、肺泡上皮和纤维化区域均观察到细胞周期蛋白D1，这与这些区域快速的细胞更新一致。在第3周时，TGF-β在肺泡巨噬细胞和上皮细胞中呈微弱染色。

结论

在博来霉素诱导的肺纤维化中，Wnt/β-连环蛋白通路被激活，并且下游基因定位于肺泡巨噬细胞、肺泡上皮和间质中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4127/3704199/e687c305ae9d/nihms275330f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4127/3704199/006c7727e227/nihms275330f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4127/3704199/0256641dbba0/nihms275330f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4127/3704199/2c0bc9f403b9/nihms275330f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4127/3704199/d5867a516a8e/nihms275330f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4127/3704199/23ee85a16f63/nihms275330f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4127/3704199/e687c305ae9d/nihms275330f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4127/3704199/006c7727e227/nihms275330f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4127/3704199/0256641dbba0/nihms275330f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4127/3704199/2c0bc9f403b9/nihms275330f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4127/3704199/d5867a516a8e/nihms275330f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4127/3704199/23ee85a16f63/nihms275330f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4127/3704199/e687c305ae9d/nihms275330f6.jpg

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