title: Carbon monoxide modulates alpha-smooth muscle actin and small proline rich-1a expression in fibrosis.
abstract: 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.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Zheng
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhou
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.forename: Sean
authors.initials: S
authors.lastname: Alber
authors.forename: Simon
authors.initials: S
authors.lastname: Watkins
authors.forename: Naftali
authors.initials: N
authors.lastname: Kaminski
authors.forename: Augustine M K
authors.initials: AM
authors.lastname: Choi
authors.forename: Danielle
authors.initials: D
authors.lastname: Morse
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000280:Administration, Inhalation; D000818:Animals; D001761:Bleomycin; D001846:Bone Development / Q000187:drug effects; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024510:Muscle Development / Q000187:drug effects; D009942:Organometallic Compounds / Q000494:pharmacology*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D054875:Ubiquitination / Q000187:drug effects
chemical_list: D000199:Actins; D055233:Cornified Envelope Proline-Rich Proteins; D009942:Organometallic Compounds; C524532:Sprr1a protein, mouse; D053773:Transforming Growth Factor beta1; C476530:tricarbonylchloro(glycinato)ruthenium(II); D001761:Bleomycin; D002248:Carbon Monoxide; D048049:Extracellular Signal-Regulated MAP Kinases