Silica nanoparticle induces pulmonary fibroblast transdifferentiation via macrophage route: Potential mechanism revealed by proteomic analysis

Recently, more and more attention has been focused on silica nanoparticles (SiNPs) as they are increasingly used in various fields. Yet, their biological effects, especially on human beings, largely remain unknown. This study was implanted to assess the biological responses in vitro elicited by human macrophages exposed to the SiNPs and to explore its toxicity and fibrosis biomarker. We found that SiNPs suppressed the viability of THP-1 cells in a dose-dependent manner while they triggered apoptosis and promoted the secretion of inflammatory factors. Next, SiNPs-induced macrophage supernatant was used to act on fibroblast (MRC-5), indicating that the expression of hydroxyproline (Hyp), α-SMA, and collagonIin MRC-5 increased after SiNPs treatment. To further explore the biomarker of fibrosis, Liquid-mass spectrometry facilitated quantitative proteomics, identified 3247 proteins, of which 791 proteins were expressed differentially in human embryonic lung fibroblasts after treated with SiNPs. In conclusion, our observations suggest that SiNPs induced THP-1-derived macrophage damage and apoptosis. Moreover, SiNPs induced macrophages to secrete cytokines that promote fibroblasts' proliferation and differentiation and changed protein expression in MRC-5 cells, regulating biological processes such as apoptosis, protein synthesis, and cell growth. Among these results, our findings could provide a basis for determining fibrosis biomarkers of silica nanoparticle exposure. •In this study, silica nanoparticle was selected as the object of study. Silica nanoparticle as a new material has been widely used, studies have indicated that its cytotoxic effect, but there are comparatively few studies on its internal exposure biomarkers.•Based on previous population studies, this study constructed an in vitro experimental model (Human macrophage-fibroblast as vitro model), systematically evaluate the cytotoxic and fibrotic effects of silica nanoparticle.•In this study, bioinformatics and proteomics were combined to further screen and analyze the differential proteins of human embryo lung fibroblasts (MRC-5) caused by silica nanoparticle exposure, so as to provide a basis for the determination of biomarkers of silica nanoparticle exposure.