Disease-specific gene expression profiling in multiple models of lung disease.
BACKGROUND
Microarray technology is widely employed for studying the molecular mechanisms underlying complex diseases. However, analyses of individual diseases or models of diseases frequently yield extensive lists of differentially expressed genes with uncertain relationships to disease pathogenesis.


OBJECTIVE
To compare gene expression changes in a heterogeneous set of lung disease models in order to identify common gene expression changes seen in diverse forms of lung pathology, as well as relatively small subsets of genes likely to be involved in specific pathophysiological processes.


METHODS
We profiled lung gene expression in 12 mouse models of infection, allergy, and lung injury. A linear model was used to estimate transcript expression changes for each model, and hierarchical clustering was used to compare expression patterns between models. Selected expression changes were verified by quantitative polymerase chain reaction.


RESULTS
A total of 24 transcripts, including many involved in inflammation and immune activation, were differentially expressed in a substantial majority (9 or more) of the models. Expression patterns distinguished three groups of models: (1) bacterial infection (n = 5), with changes in 89 transcripts, including many related to nuclear factor-kappaB signaling, cytokines, chemokines, and their receptors; (2) bleomycin-induced diseases (n = 2), with changes in 53 transcripts, including many related to matrix remodeling and Wnt signaling; and (3) T helper cell type 2 (allergic) inflammation (n = 5), with changes in 26 transcripts, including many encoding epithelial secreted molecules, ion channels, and transporters.


CONCLUSIONS
This multimodel dataset highlights novel genes likely involved in various pathophysiological processes and will be a valuable resource for the investigation of molecular mechanisms underlying lung disease pathogenesis.
Lewis
Christina C
CC
Cincinnati Children's Hospital Medical Center/Division of Immunobiology, 3333 Burnet Avenue, MLC 7038, Cincinnati, OH 45229, USA. cclewis@cinci.rr.com
Yang
Jean Yee Hwa
JY
Huang
Xiaozhu
X
Banerjee
Suman K
SK
Blackburn
Michael R
MR
Baluk
Peter
P
McDonald
Donald M
DM
Blackwell
Timothy S
TS
Nagabhushanam
Vijaya
V
Peters
Wendy
W
Voehringer
David
D
Erle
David J
DJ
D000818:Animals; D001249:Asthma / Q000235:genetics*; D001761:Bleomycin / Q000633:toxicity; D054377:Chemokine CXCL12 / Q000032:analysis / Q000235:genetics; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D016014:Linear Models; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D011014:Pneumonia / Q000235:genetics*; D011336:Probability; D011658:Pulmonary Fibrosis / Q000235:genetics*; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
D054377:Chemokine CXCL12; D001761:Bleomycin