Carbon Monoxide Modulates α–Smooth Muscle Actin and Small Proline Rich-1a Expression in Fibrosis

• DOI: 10.1165/rcmb.2007-0401oc
• Publication Date: 2008-12-20T01:12:48Z
• Authors: Liang Zheng; Zhihong Zhou; Ling Lin; Sean Alber; Simon Watkins; Naftali Kaminski; Augustine M. K. Choi; Danielle Morse
• Keywords: Male; 0301 basic medicine; Carbon Monoxide; Bone Development; Cell Death; Dose-Response Relationship, Drug; MAP Kinase Signaling System; Gene Expression Profiling; Fibroblasts; Actins; Mice, Inbred C57BL; Bleomycin; Disease Models, Animal; Mice; 03 medical and health sciences; Cell Movement; Cornified Envelope Proline-Rich Proteins; Administration, Inhalation; Animals; Extracellular Signal-Regulated MAP Kinases; Lung; Cells, Cultured

Carbon monoxide (CO) is a biologically active molecule produced in the body by the stress-inducible enzyme, heme oxygenase. We have 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 transforming growth factor-beta(1) and CO. The most highly differentially expressed categories of genes included those related to muscular system development and the small proline-rich family of proteins. We confirmed in vitro, and in an in vivo bleomycin model of lung fibrosis, that CO suppresses alpha-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.