MitoQ ameliorates PM2.5-induced pulmonary fibrosis through regulating the mitochondria DNA homeostasis

Chemosphere. 2023 Jul:330:138745. doi: 10.1016/j.chemosphere.2023.138745. Epub 2023 Apr 21.

Abstract

Pulmonary fibrosis is a severe pulmonary disease, and may related to PM2.5 exposure. Our study aims to explore the pathogenesis of PM2.5-induced pulmonary fibrosis, and MitoQ protective effect in this process. Our results find that inflammatory cells aggregation and pulmonary fibrosis in mice lung after PM2.5 exposure. Moreover, Collagen I/III overproduction, EMT and TGF-β1/Smad2 pathway activation in mice lung and BEAS-2B after PM2.5 exposure. Fortunately, these changes were partially ameliorated after MitoQ treatment. Meanwhile, severe oxidative stress, mitochondrial homeostasis imbalance, overproduction of 8-oxoG (7,8-dihydro-8-oxoguanine), as well as the inhibition of SIRT3/OGG1 pathway have founded in mice lung or BEAS-2B after PM2.5 exposure, which were alleviated by MitoQ treatment. Collectively, our study found that oxidative stress, especially mitochondrial oxidative stress participates in the PM2.5-induced pulmonary fibrosis, and MitoQ intervention had a protective effect on this progress. Moreover, mitochondrial DNA homeostasis might participate in the pulmonary fibrosis caused by PM2.5 exposure. Our study provides a novel pathogenesis of PM2.5-caused pulmonary fibrosis and a possible targeted therapy for the pulmonary diseases triggered by PM2.5.

Keywords: MitoQ; Mitochondrial DNA damage; Oxidative stress; PM(2.5); Pulmonary fibrosis.

MeSH terms

  • Animals
  • DNA, Mitochondrial / metabolism
  • Homeostasis
  • Mice
  • Mitochondria / metabolism
  • Oxidative Stress
  • Particulate Matter / adverse effects
  • Pulmonary Fibrosis* / chemically induced

Substances

  • mitoquinone
  • DNA, Mitochondrial
  • Particulate Matter