Carbon monoxide modulates α-smooth muscle actin and small proline rich-1a expression in fibrosis

Carbon monoxide (CO) is a biologically active molecule produced in the body by the stress-inducible enzyme, heme oxygenase.Wehave previously shown that CO suppresses fibrosis in a murine bleomycin model. To investigate the mechanisms by which CO opposes fibrogenesis, we performed gene expression profiling of fibroblasts treated with transforminggrowthfactor-β₁ and CO. The mosthighly differentially expressed categories of genes included those related to muscular system development and the small proline-rich family of proteins.Weconfirmed in vitro, and in an in vivo bleomycin model of lung fibrosis, that CO suppresses α-smooth muscle actin expression and enhances small proline-rich protein-1a expression. We further show that these effects of CO depend upon signaling via the extracellular signal-regulated kinase pathway. Our results demonstrate novel transcriptional targets for CO and further elucidate the mechanism by which CO suppresses fibrosis.