NOX4 modulates macrophage phenotype and mitochondrial biogenesis in asbestosis.
JCI Insight
; 4(16)2019 08 22.
Article
em En
| MEDLINE
| ID: mdl-31434799
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Asbestose
/
Biogênese de Organelas
/
Macrófagos Alveolares
/
NADPH Oxidase 4
/
Macrófagos
Limite:
Adult
/
Aged
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2019
Tipo de documento:
Article