Time-course transcriptomic alterations reflect the pathophysiology of polyhexamethylene guanidine phosphate-induced lung injury in rats.

Humidifier-disinfectant-induced lung injury is a new syndrome associated with a high mortality rate and characterized by severe hypersensitivity pneumonitis, acute interstitial pneumonia, or acute respiratory distress syndrome. Polyhexamethylene guanidine phosphate (PHMG-P), a guanidine-based antimicrobial agent, is a major component associated with severe lung injury. In-depth studies are needed to determine how PHMG-P affects pathogenesis at the molecular level. Therefore, in this study, we analyzed short-term (4 weeks) and long-term (10 weeks) PHMG-P-exposure-specific gene-expression patterns in rats to improve our understanding of time-dependent changes in fibrosis. Gene-expression profiles were analyzed in rat lung tissues using DNA microarrays and bioinformatics tools. Clustering analysis of gene-expression data showed different gene-alteration patterns in the short- and long-term exposure groups and higher sensitivity to gene-expression changes in the long-term exposure group than in the short-term exposure group. Supervised analysis revealed 34 short-term and 335 long-term exposure-specific genes, and functional analysis revealed that short-term exposure-specific genes were involved in PHMG-P-induced initial inflammatory responses, whereas long-term exposure-specific genes were involved in PHMG-P-related induction of chronic lung fibrosis. The results of transcriptomic analysis were consistent with lung histopathology results. These findings indicated that exposure-time-specific changes in gene expression closely reflected time-dependent pathological changes in PHMG-P-induced lung injury.