Temporal modulation of cuproptosis and autophagy mediates nanographene-driven pulmonary fibrosis progression.

Abstract

Graphene nanoparticles are increasingly used in materials manufacturing, pollutant treatment, energy storage, and electronic devices, and the potential risk of occupational and environmental exposure is a concern. The mechanisms of lung fibrosis induced by nano-graphene with different properties are complex. In addition, multiple modes of programmed cell death (PCD) occur during lung fibrosis, and whether cuproptosis and autophagy exert regulatory effects during the progression of lung fibrosis induced by nano-graphene remains undocumented. In this study, we constructed mouse models with varying doses of graphene and exposure durations. We observed the dynamics of pathological changes in lung histology and the time-series expression of biomarkers. We discovered that graphene could deposit in lung tissue, leading to the pathological manifestations of pulmonary fibrosis; this was coincident with elevated copper ion concentration, cellular cuproptosis, and excessive autophagy. In short, our results may contribute to further elucidation of the potential respiratory toxic effects and mechanisms of graphene, and to the early development of targeted preventive and control measures by providing new ideas and reference points.