Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 97, Issue 4, Pages 1778-1783Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.97.4.1778
Keywords
cluster analysis; oligonucleotide arrays; alpha v beta 6; bleomycin; pulmonary fibrosis
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Funding
- NHLBI NIH HHS [HL33259, HL47412, R37 HL053949, F32 HL009793, R01 HL053949] Funding Source: Medline
- NIAID NIH HHS [AI33259] Funding Source: Medline
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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.
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