Molecular monitoring of bleomycin-induced pulmonary fibrosis by cDNA microarray-based gene expression profiling

Pulmonary fibrosis is a progressive disorder whose molecular pathology is p oorly understood. Here we developed an in-house cDNA microarray ("lung chip ") originating from a lung-normalized cDNA library. By using this lung chip , we analyzed global gene expression in a murine model of bleomycin-induced fibrosis and selected 82 genes that differed by more than twofold intensit y in at least one pairwise comparison with controls. Cluster analysis of th ese selected genes showed that the expression of genes associated with infl ammation reached maximum levels at 5 days after bleomycin administration, w hile genes involved in the development of fibrosis increased gradually up t o 14 days after bleomycin treatment. These changes in gene expression signa ture were well correlated with observed histopathological changes. The resu lts show that microarray analysis of animal disease models is a powerful ap proach to understanding the gene expression programs that underlie these di sorders. (C) 2001 Academic Press.