Differential gene expression in the initiation and progression of nickel-induced acute lung injury

Acute lung injury, an often fatal condition, can result from a wide range o f insults leading to a complex series of biologic responses. Despite extens ive research, questions remain about the interplay of the factors involved and their role in acute lung injury. We proposed that assessing the tempora l and functional relationships of differentially expressed genes after pulm onary insult would reveal novel interactions in the progression of acute lu ng injury. Specifically, 8,734 sequence-verified murine complementary DNAs were analyzed in mice throughout the initiation and progression of acute lu ng injury induced by particulate nickel sulfate. This study revealed the ex pression patterns of genes previously associated with acute lung injury in relationship to one another and also uncovered changes in expression of a n umber of genes not previously associated with acute lung injury. The overal l pattern of gene expression was consistent with oxidative stress, hypoxia, cell proliferation, and extracellular matrix repair, followed by a marked decrease in pulmonary surfactant proteins. Also, expressed sequence tags (E STs), with nominal homology to known genes, displayed similar expression pa tterns to those of known genes, suggesting possible roles for these ESTs in the pulmonary response to injury. Thus, this analysis of the progression a nd response to acute lung injury revealed novel gene expression patterns.