دورية أكاديمية
NOX4 modulates macrophage phenotype and mitochondrial biogenesis in asbestosis.
العنوان: | NOX4 modulates macrophage phenotype and mitochondrial biogenesis in asbestosis. |
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المؤلفون: | He C; Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, and., Larson-Casey JL; Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, and., Davis D; Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, and., Hanumanthu VS; Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA., Longhini ALF; Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA., Thannickal VJ; Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, and.; Birmingham Veterans Administration Medical Center, Birmingham, Alabama, USA., Gu L; Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, and., Carter AB; Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, and.; Birmingham Veterans Administration Medical Center, Birmingham, Alabama, USA. |
المصدر: | JCI insight [JCI Insight] 2019 Aug 22; Vol. 4 (16). Date of Electronic Publication: 2019 Aug 22. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. |
اللغة: | English |
بيانات الدورية: | Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]- |
مواضيع طبية MeSH: | Organelle Biogenesis*, Asbestosis/*metabolism , Macrophages/*physiology , Macrophages, Alveolar/*physiology , NADPH Oxidase 4/*metabolism, Adult ; Aged ; Animals ; Cell Line ; Cell Polarity ; Female ; Fibrosis ; Humans ; Male ; Mice ; Middle Aged ; Phenotype ; Reactive Oxygen Species/metabolism |
مستخلص: | Macrophage activation is implicated in the development of pulmonary fibrosis by generation of profibrotic molecules. Although NADPH oxidase 4 (NOX4) is known to contribute to pulmonary fibrosis, its effects on macrophage activation and mitochondrial redox signaling are unclear. Here, we show that NOX4 is crucial for lung macrophage profibrotic polarization and fibrotic repair after asbestos exposure. NOX4 was elevated in lung macrophages from subjects with asbestosis, and mice harboring a deletion of NOX4 in lung macrophages were protected from asbestos-induced fibrosis. NOX4 promoted lung macrophage profibrotic polarization and increased production of profibrotic molecules that induce collagen deposition. Mechanistically, NOX4 further augmented mitochondrial ROS production and induced mitochondrial biogenesis. Targeting redox signaling and mitochondrial biogenesis prevented the profibrotic polarization of lung macrophages by reducing the production of profibrotic molecules. These observations provide evidence that macrophage NOX4 is a potentially novel therapeutic target to halt the development of asbestos-induced pulmonary fibrosis. |
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معلومات مُعتمدة: | R56 ES027464 United States ES NIEHS NIH HHS; I01 CX001715 United States CX CSRD VA; P30 AR048311 United States AR NIAMS NIH HHS; T32 HL105346 United States HL NHLBI NIH HHS; R01 ES015981 United States ES NIEHS NIH HHS |
فهرسة مساهمة: | Keywords: Bioenergetics; Immunology; Macrophages; Mitochondria; Pulmonology |
المشرفين على المادة: | 0 (Reactive Oxygen Species) EC 1.6.3.- (NADPH Oxidase 4) EC 1.6.3.- (NOX4 protein, human) EC 1.6.3.- (Nox4 protein, mouse) |
تواريخ الأحداث: | Date Created: 20190823 Date Completed: 20200917 Latest Revision: 20200917 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC6777818 |
DOI: | 10.1172/jci.insight.126551 |
PMID: | 31434799 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2379-3708 |
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DOI: | 10.1172/jci.insight.126551 |