title: Involvement of selenoprotein P in the regulation of redox balance and myofibroblast viability in idiopathic pulmonary fibrosis.
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.
authors.affiliation: Department of Biomolecular Science, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan.
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Kabuyama
authors.forename: Kengo
authors.initials: K
authors.lastname: Oshima
authors.forename: Takuya
authors.initials: T
authors.lastname: Kitamura
authors.forename: Miwako
authors.initials: M
authors.lastname: Homma
authors.forename: Junko
authors.initials: J
authors.lastname: Yamaki
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Munakata
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Homma
mesh_terms: D002470:Cell Survival / Q000502:physiology; D005347:Fibroblasts / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008054:Lipid Peroxides / Q000235:genetics / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051149:Selenoprotein P / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D008054:Lipid Peroxides; D051149:Selenoprotein P; D048670:MAP Kinase Kinase 4