Gene expression in developing fibrotic lesions in tracheas of chlorine-exposed mice

Chlorine is a widely used industrial chemical that is also considered a chemical threat agent. Inhalation of chlorine gas can cause acute injury to the respiratory tract, including the death of airway epithelial cells. Failure to efficiently repair the epithelial damage is associated with long-term respiratory abnormalities, including airway fibrosis. We previously developed a model of airway injury in which mice exposed to chlorine gas exhibit epithelial damage and develop fibrosis in large airways. In the present study, we measured gene expression in developing fibrotic lesions isolated from chlorine-exposed mice 4 days after exposure and compared to expression in corresponding areas from unexposed mice. Mesenchymal tissue was isolated by laser-capture microdissection to limit the analysis to the developing fibrotic lesions. The 4-day time point was chosen in an attempt to identify early profibrotic signaling events because at this time fibroblast proliferation has commenced but the fibrotic scar has not yet formed. Male FVB/NJ mice 9 weeks of age were exposed to 235 ppm chlorine for 1 hr. Tracheas were collected from 5 chlorine-exposed mice 4 days after exposure and from 5 unexposed mice. Laser-capture microdissection was used to collect mesenchymal tissue from frozen sections of tracheas. RNA prepared from the isolated tissue was amplified, labeled, and hybridized to Affymetrix microarrays.