Silica nanoparticles induce pulmonary autophagy dysfunction and epithelial-to-mesenchymal transition via p62/NF-κB signaling pathway

It has been reported that silica nanoparticles (SiNPs) could cause epithelial-to-mesenchymal transition (EMT), but the specific mechanism is still unclear. Thus, the purpose of this study was to investigate the underlying mechanisms of pulmonary EMT after subacute exposure to SiNPs. The results showed intratracheal instillation of SiNPs increased the pulmonary MDA content, while decreased the activity of SOD and GSH-Px in rats. Western blot analysis demonstrated that SiNPs induced autophagy dysfunction via the upregulation of p62. Meanwhile, the inflammation cytokines (TNF-alpha, IL-18, IL-1 beta) were released in rat lung. Immunohistochemistry and western blot assays both showed that SiNPs could regulate the related protein biomarkers of EMT through decreasing Ecadherin and increasing vimentin in a dose-dependent manner. Besides, SiNPs activated the proteins expression involved in p62/NF-kappa B signaling pathway, whereas the pulmonary EMT induced by SiNPs was significantly dampened after the knock down of p62. In this study, we illustrated that subacute exposure to SiNPs could trigger the autophagy dysfunction and pulmonary inflammation, further lead to EMT via activating the p62/NF-kappa B signaling pathway. Our findings provide new molecular evidence for SiNPs-induced pulmonary toxicity.

Automated summary

In this study, we found that subacute exposure to silica nanoparticles (SiNPs) can trigger autophagy dysfunction and pulmonary inflammation, leading to epithelial-to-mesenchymal transition (EMT) through activation of the p62/NF-kappa B signaling pathway.