Molecular monitoring of bleomycin-induced pulmonary fibrosis by cDNA microarray-based gene expression profiling.
Pulmonary fibrosis is a progressive disorder whose molecular pathology is poorly 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 intensity in at least one pairwise comparison with controls. Cluster analysis of these selected genes showed that the expression of genes associated with inflammation reached maximum levels at 5 days after bleomycin administration, while genes involved in the development of fibrosis increased gradually up to 14 days after bleomycin treatment. These changes in gene expression signature were well correlated with observed histopathological changes. The results show that microarray analysis of animal disease models is a powerful approach to understanding the gene expression programs that underlie these disorders.
Katsuma
S
S
Department of Molecular Cell Pharmacology, National Children's Medical Research Center, 3-35-31 Taishido, Setagaya-ku, Tokyo, 154-8509, Japan.
Nishi
K
K
Tanigawara
K
K
Ikawa
H
H
Shiojima
S
S
Takagaki
K
K
Kaminishi
Y
Y
Suzuki
Y
Y
Hirasawa
A
A
Ohgi
T
T
Yano
J
J
Murakami
Y
Y
Tsujimoto
G
G
D000818:Animals; D001761:Bleomycin / Q000494:pharmacology*; D003001:Cloning, Molecular; D016000:Cluster Analysis; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D012333:RNA, Messenger; D001761:Bleomycin