Silicon Carbide Nanoparticles Induce Pulmonary Fibrosis by Promoting Macrophage Apoptosis through Parkin-Mediated Mitophagy Disruption and the Intervention Effect of Emodin

Silicon carbide nanoparticles (SiC-NPs), an emerging class of nanomaterials, have garnered extensive applications in industrial and biomedical fields. The escalating use of SiC-NPs engenders substantial concerns regarding the potential biosafety implications. Previous studies indicate the association between silicon carbide exposure and elevated incidence of pulmonary fibrosis. However, the underlying mechanisms remain insufficiently elucidated. In this study, we investigated the role of SiC-NPs in pulmonary fibrosis development, employing THP-1-derived macrophages (THP-M) for in vitro experimentation and C57BL/6 mice for in vivo analyses. Our study demonstrated that exposure to SiC-NPs led to the production of reactive oxygen species (ROS) and mitochondrial damage in macrophages. This sequence of events impaired mitophagy and subsequently triggered macrophage apoptosis, ultimately contributing to the pathogenesis of pulmonary fibrosis. Mechanistically, we elucidated that SiC-NPs promoted the ubiquitin-mediated degradation of Parkin, resulting in dysregulated mitophagy. Furthermore, we revealed that emodin treatment mitigated SiC-NPs-induced pulmonary fibrosis by restoring Parkin expression. Our study provides novel insights into the detrimental effects and underlying mechanisms of SiC-NPs in pulmonary fibrosis, as well as highlighting the therapeutic potential of emodin.