title: Signalling pathways from NADPH oxidase-4 to idiopathic pulmonary fibrosis.
abstract: This review focuses on the roles of NADPH oxidase/NOX proteins in idiopathic pulmonary fibrosis (IPF) pathophysiology and in the signalling pathways involved in IPF. NOX proteins are membrane-associated multi-unit enzymes that catalyze the reduction of oxygen using NADPH as an electron donor. Recent studies indicate that NOX4 is induced in pulmonary fibroblasts in response to TGF-β. TGF-β or PDGF induce myofibroblast proliferation, differentiation, migration, contractility and extracellular matrix production, through NOX4 and reactive oxygen species dependent SMAD2/3 phosphorylation. NOX4 is increased in pulmonary fibroblasts from IPF patients and deletion of Nox4 in mice prevents bleomycin-induced pulmonary fibrosis. These data strongly suggest that targeting of NOX4 could be a step forward in the treatment of fibrotic lung diseases, by specifically targeting myofibroblasts, a major player in this disease.
authors.affiliation: INSERM, Unité 700, Paris, France. bruno.crestani@bch.aphp.fr
authors.forename: Bruno
authors.initials: B
authors.lastname: Crestani
authors.forename: Valérie
authors.initials: V
authors.lastname: Besnard
authors.forename: Jorge
authors.initials: J
authors.lastname: Boczkowski
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000201:enzymology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D017382:Reactive Oxygen Species; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; C422943:Nox4 protein, mouse