Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis
Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis
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DOI：
10.1073/pnas.97.4.1778
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发表时间：
2000-02-15
影响因子：
11.1
通讯作者：
Heller, RA
中科院分区：
文献类型：
--
作者：
Kaminski, N;Allard, JD;Heller, RA
肺纤维化的分子机制尚不清楚。我们使用寡核苷酸阵列分析了两种易感小鼠品系（129 和 C57BL/6）中博莱霉素（一种引起肺部炎症和纤维化的药物）对肺纤维化的基因表达程序。然后，我们将这些小鼠的基因表达模式与 129 只携带上皮限制性整合素 β 6 亚基（β 6(-/-)）零突变的小鼠进行了比较，这些小鼠发生炎症，但免受肺损伤。纤维化，聚类分析确定了参与炎症和纤维化反应的两组不同的基因。博莱霉素给药后多个时间点的基因表达分析揭示了表征每种反应的基因子集的连续诱导。这一综合数据集的可用性应加速制定更有效的干预策略，以干预肺部和其他器官纤维化疾病发展的各个阶段。
The molecular mechanisms of pulmonary fibrosis are poorly understood. We have used oligonucleotide arrays to analyze the gene expression programs that underlie pulmonary fibrosis in response to bleomycin, a drug that causes lung inflammation and fibrosis, in two strains of susceptible mice (129 and C57BL/6), We then compared the gene expression patterns in these mice with 129 mice carrying a null mutation in the epithelial-restricted integrin beta 6 subunit (beta 6(-/-)), which develop inflammation but are protected from pulmonary fibrosis, Cluster analysis identified two distinct groups of genes involved in the inflammatory and fibrotic responses. Analysis of gene expression at multiple time points after bleomycin administration revealed sequential induction of subsets of genes that characterize each response. The availability of this comprehensive data set should accelerate the development of more effective strategies for intervention at the various stages in the development of fibrotic diseases of the lungs and other organs.