Carbon monoxide modulates alpha-smooth muscle actin and small proline rich-1a expression in fibrosis. Academic Article uri icon

Overview

MeSH

  • Administration, Inhalation
  • Animals
  • Bleomycin
  • Bone Development
  • Cell Death
  • Cell Movement
  • Cells, Cultured
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Extracellular Signal-Regulated MAP Kinases
  • Gene Expression Profiling
  • MAP Kinase Signaling System
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Development
  • Time Factors
  • Transforming Growth Factor beta1
  • Ubiquitination

MeSH Major

  • Actins
  • Carbon Monoxide
  • Cornified Envelope Proline-Rich Proteins
  • Fibroblasts
  • Lung
  • Organometallic Compounds
  • Pulmonary 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.

publication date

  • July 2009

has subject area

  • Actins
  • Administration, Inhalation
  • Animals
  • Bleomycin
  • Bone Development
  • Carbon Monoxide
  • Cell Death
  • Cell Movement
  • Cells, Cultured
  • Cornified Envelope Proline-Rich Proteins
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Extracellular Signal-Regulated MAP Kinases
  • Fibroblasts
  • Gene Expression Profiling
  • Lung
  • MAP Kinase Signaling System
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Development
  • Organometallic Compounds
  • Pulmonary Fibrosis
  • Time Factors
  • Transforming Growth Factor beta1
  • Ubiquitination

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2701963

Digital Object Identifier (DOI)

  • 10.1165/rcmb.2007-0401OC

PubMed ID

  • 19097987

Additional Document Info

start page

  • 85

end page

  • 92

volume

  • 41

number

  • 1