| A key role for NOX4 in epithelial cell death during development of lung fibrosis. | |
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MedLine Citation:
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PMID: 21391892 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The pathogenesis of pulmonary fibrosis is linked to oxidative stress, possibly generated by the ROS generating NADPH oxidase NOX4. Epithelial cell death is a crucial early step in the development of the disease, followed only later by the fibrotic stage. We demonstrate that in lungs of patients with idiopathic lung fibrosis, there is strong expression of NOX4 in hyperplastic alveolar type II cells. To study a possible causative role of NOX4 in the death of alveolar cells, we have generated NOX4-deficient mice. Three weeks after administration of bleomycin, wild-type mice developed massive fibrosis while NOX4-deficient mice displayed almost normal lung histology, and only little Smad2 phosphorylation and accumulation of myofibroblasts. However, the protective effects of NOX4 deficiency preceded the fibrotic stage. Indeed, at day 7 after bleomycin, lungs of wild-type mice showed massive increase in epithelial cell apoptosis and inflammation. In NOX4-deficient mice, no increase in apoptosis was observed, whereas inflammation was comparable to wild-type. In vitro, NOX4-deficient primary alveolar epithelial cells exposed to TGF-b1 did not generate ROS and were protected from apoptosis. Acute treatment with the NOX inhibitors also blunted TGF-b1-induced apoptosis. ROS generation by NOX4 is a key player in epithelial cell death leading to pulmonary fibrosis. |
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Authors:
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Stephanie Carnesecchi; Christine Deffert; Yves Donati; Olivier Basset; Boris Hinz; Olivier Preynat-Seauve; Cecile Guichard; Jack L Arbiser; Botond Banfi; Jean-Claude Pache; Constance Barazzone; Karl-Heinz Krause |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-11 |
Journal Detail:
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Title: Antioxidants & redox signaling Volume: - ISSN: 1557-7716 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100888899 Medline TA: Antioxid Redox Signal Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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CMU, pathology -immunology and pediatrics, 1 rue michel servet, geneva, Switzerland, 1211; stephanie.carnesecchi@unige.ch. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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