Modification of the rat airway explant transcriptome by cigarette smoke

Although a number of animal model studies have addressed changes in gene expression in the parenchyma and their relationship to emphysema, much less is known about the pathogenesis of cigarette smoke-induced small airway remodeling. In this study the authors exposed rat tracheal explants, a model of the airway wall, to whole smoke for 15 min, and then cultured the explants in air. The airway transcriptome was evaluated using RAE 230_2 gene chips. By 2 h after starting smoke exposure, expression levels of 502 genes were differentially expressed by more than 1.5 times (p < .01 or less) and by 24 h 1870 genes were significantly changed up or down. These included genes involved in antioxidant protection, epithelial defense and remodeling, inflammatory mediators and transcription factors, and a number of unexpected genes, including the matrix metalloproteinase (MMP)-12 inducer, tachykinin-1 (substance P). Pretreatment of the explants with 1 x 10