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

Toxicol In Vitro. 2021 Oct:76:105220. doi: 10.1016/j.tiv.2021.105220. Epub 2021 Jul 14.

Abstract

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.

Keywords: Bioinformatic analysis; Proteomics; Silicon dioxide nanoparticle cytotoxicity.

MeSH terms

  • Cell Line
  • Cell Survival / drug effects
  • Cell Transdifferentiation / drug effects
  • Cytokines / metabolism
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibroblasts / physiology
  • Humans
  • Lung / cytology
  • Lung / embryology
  • Macrophages / drug effects
  • Nanoparticles / toxicity*
  • Proteomics
  • Silicon Dioxide / toxicity*

Substances

  • Cytokines
  • Silicon Dioxide