These observations provide evidence that macrophage NOX4 is a potentially novel therapeutic target to halt the development of asbestos-induced pulmonary fibrosis.
Magnesium isoglycyrrhizinate ameliorates radiation-induced pulmonary fibrosis by inhibiting fibroblast differentiation via the p38MAPK/Akt/Nox4 pathway.
In this chapter, we present methods and procedures to apply the aging model of lung fibrosis in mice that will allow interrogation of myofibroblast functions and the expression and activity of NOX4 in cells.
We found that Ang-(1-7) reduced hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) concentration, protein levels of NOX4, and autophagy impairment, as well as improving lung fibrosis induced by smoking stimulation in vivo.
Collectively, these results suggest that LYCAT is a negative regulator of TGF-β-induced lung fibroblast differentiation by modulation of mitochondrial superoxide and NOX4 dependent H<sub>2</sub>O<sub>2</sub> generation, and this may serve as a potential therapeutic target for human lung fibrosis.
Relevant to human pulmonary fibrosis, idiopathic PF specimens showed significantly higher NOX4 RNA expression and scant HDAC4 staining within nuclei of fibroblast foci myofibroblasts.
These results suggest that AZM suppresses NOX4 by promoting proteasomal degradation, resulting in inhibition of TGFB-induced myofibroblast differentiation and lung fibrosis development.
Furthermore, the significant overexpression of NADPH oxidase 4 (NOX4) was observed in BLM-induced pulmonary fibrosis, which was inhibited by Sch B or/and GA. Our study reveals that the synergistic protection by Sch B and GA against BLM-induced pulmonary fibrosis is correlated to its anti-inflammatory, anti-oxidative and anti-fibrotic properties, involving inhibition of TGF-β1/Smad2 signaling pathways and overexpression of NOX4.