Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis

The molecular mechanisms of pulmonary fibrosis are poorly understood. We ha ve used oligonucleotide arrays to analyze the gene expression programs that underlie pulmonary fibrosis in response to bleomycin, a drug that causes l ung 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 bet a 6 subunit (beta 6(-/-)), which develop inflammation but are protected fro m pulmonary fibrosis, Cluster analysis identified two distinct groups of ge nes involved in the inflammatory and fibrotic responses. Analysis of gene e xpression at multiple time points after bleomycin administration revealed s equential induction of subsets of genes that characterize each response. Th e availability of this comprehensive data set should accelerate the develop ment of more effective strategies for intervention at the various stages in the development of fibrotic diseases of the lungs and other organs.