Abstract
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.
Original language | English (US) |
---|---|
Pages (from-to) | 85-92 |
Number of pages | 8 |
Journal | American Journal of Respiratory Cell and Molecular Biology |
Volume | 41 |
Issue number | 1 |
DOIs | |
State | Published - Jul 1 2009 |
Keywords
- Carbon monoxide
- Heme oxygenase-1
- Lung fibrosis
- Small proline-rich protein
- α-smooth muscle actin
ASJC Scopus subject areas
- Molecular Biology
- Pulmonary and Respiratory Medicine
- Clinical Biochemistry
- Cell Biology