Pregnancy exposure to carbon black nanoparticles exacerbates bleomycin-induced lung fibrosis in offspring via disrupting LKB1-AMPK-ULK1 axis-mediated autophagy

Abstract

Accumulating evidence shows that carbon black nanoparticles (CBNPs) (one of the most used nanoparticles) can induce toxicity via induction of inflammation, oxidative stress and genotoxicity in vitro and in vivo, and epidemiological studies have indicated that the possible correlation between maternal immune activation and risk of developing neuropsychiatric disorder in the offspring. However, whether pregnancy exposure of CBNPs (Pr-CBNPs) enhances the susceptibility to bleomycin (BLM)-induced lung fibrosis in offspring is unknown. Herein, we demonstrated that Pr-CBNPs during gestational day 9-18 via intranasal administration could confer enhanced susceptibility to BLM-induced fibrotic response in offspring, including deteriorative lung pathologic changes and more collagen deposition. Intriguingly, we found that Pr-CBNPs repressed the activation of autophagy (an anti-fibrotic mechanism), which was moderately activated in offspring from mock group. Moreover, Pr-CBNPs was likely to disrupt the LKB1-AMPK-ULK1 axis (a key regulatory pathway for autophagy induction). In summary, this study provides the first evidence that pregnancy exposure to CBNPs can exacerbate BLM-induced lung fibrotic response in offspring probably through disruption of LKB1-AMPK-ULK1 axis-mediated autophagy.

Keywords: Autophagy; Carbon black nanoparticles; Lung fibrosis; Offspring; Pregnancy exposure.