Involvement of selenoprotein P in the regulation of redox balance and myofibroblast viability in idiopathic pulmonary fibrosis
Open Access
- 2 November 2007
- journal article
- Published by Wiley in Genes to Cells
- Vol. 12 (11), 1235-1244
- https://doi.org/10.1111/j.1365-2443.2007.01127.x
Abstract
Idiopathic pulmonary fibrosis (IPF), a chronic progressive lung disease of unknown etiology, is characterized by the expansion of myofibroblasts and abnormal deposition of extracellular matrix in the lung parenchyma. To elucidate the molecular mechanisms that lead to IPF, we analyzed myofibroblasts established from patients with IPF by oligonucleotide microarrays. Gene expression profiles clearly suggested that lipid peroxidation is enhanced in myofibroblasts, which was confirmed by measuring cellular lipid hydroperoxides. One of the most highly up‐regulated proteins in myofibroblasts was selenoprotein P, an antioxidant protein not previously associated with IPF. Subsequent analysis demonstrated that selenoprotein P reduces lipid hydroperoxides and maintains the viability of myofibroblasts. Thus, our results reveal a novel pathophysiologic function of myofibroblasts as a generator of lipid hydroperoxides, and a self‐defense mechanism against self‐generated oxidative stress.Keywords
This publication has 32 references indexed in Scilit:
- Protective effect of α‐tocopherol on oxidative stress in experimental pulmonary fibrosis in ratsCell Biochemistry and Function, 2006
- Evolving Concepts of Apoptosis in Idiopathic Pulmonary FibrosisProceedings of the American Thoracic Society, 2006
- Current Perspectives on the Treatment of Idiopathic Pulmonary FibrosisProceedings of the American Thoracic Society, 2006
- Lipid peroxidation: Mechanisms, inhibition, and biological effectsBiochemical and Biophysical Research Communications, 2005
- Modulation of Prosurvival Signaling in Fibroblasts by a Protein Kinase Inhibitor Protects against Fibrotic Tissue InjuryThe American Journal of Pathology, 2005
- Hydrogen peroxide is a diffusible paracrine signal for the induction of epithelial cell death by activated myofibroblastsThe FASEB Journal, 2005
- Expression of the thioredoxin system in interstitial lung diseaseThe Journal of Pathology, 2003
- A Comparative Study on the Hydroperoxide and Thiol Specificity of the Glutathione Peroxidase Family and Selenoprotein PPublished by Elsevier BV ,2002
- Oxidative Protein Cross-linking Reactions Involvingl-Tyrosine in Transforming Growth Factor-β1-stimulated FibroblastsPublished by Elsevier BV ,2001
- Increased oxidation of extracellular glutathione by bronchoalveolar inflammatory cells in diffuse fibrosing alveolitisEuropean Respiratory Journal, 1995