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NOX4 modulates macrophage phenotype and mitochondrial biogenesis in asbestosis.
JCI Insight 2019; 4(16)JI

Abstract

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.

Authors+Show Affiliations

Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, and.Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, and.Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, and.Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA.Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA.Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, and. Birmingham Veterans Administration Medical Center, Birmingham, Alabama, USA.Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, and.Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, and. Birmingham Veterans Administration Medical Center, Birmingham, Alabama, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31434799

Citation

He, Chao, et al. "NOX4 Modulates Macrophage Phenotype and Mitochondrial Biogenesis in Asbestosis." JCI Insight, vol. 4, no. 16, 2019.
He C, Larson-Casey JL, Davis D, et al. NOX4 modulates macrophage phenotype and mitochondrial biogenesis in asbestosis. JCI Insight. 2019;4(16).
He, C., Larson-Casey, J. L., Davis, D., Hanumanthu, V. S., Longhini, A. L. F., Thannickal, V. J., ... Carter, A. B. (2019). NOX4 modulates macrophage phenotype and mitochondrial biogenesis in asbestosis. JCI Insight, 4(16), doi:10.1172/jci.insight.126551.
He C, et al. NOX4 Modulates Macrophage Phenotype and Mitochondrial Biogenesis in Asbestosis. JCI Insight. 2019 Aug 22;4(16) PubMed PMID: 31434799.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NOX4 modulates macrophage phenotype and mitochondrial biogenesis in asbestosis. AU - He,Chao, AU - Larson-Casey,Jennifer L, AU - Davis,Dana, AU - Hanumanthu,Vidya Sagar, AU - Longhini,Ana Leda F, AU - Thannickal,Victor J, AU - Gu,Linlin, AU - Carter,A Brent, Y1 - 2019/08/22/ PY - 2018/12/03/received PY - 2019/07/16/accepted PY - 2019/8/23/entrez PY - 2019/8/23/pubmed PY - 2019/8/23/medline KW - Bioenergetics KW - Immunology KW - Macrophages KW - Mitochondria KW - Pulmonology JF - JCI insight JO - JCI Insight VL - 4 IS - 16 N2 - 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. SN - 2379-3708 UR - https://www.unboundmedicine.com/medline/citation/31434799/NOX4_modulates_macrophage_phenotype_and_mitochondrial_biogenesis_in_asbestosis L2 - https://doi.org/10.1172/jci.insight.126551 DB - PRIME DP - Unbound Medicine ER -