Cardamonin inhibits silicosis development through the PI3K-AKT signaling pathway

Abstract

Silicosis is one of the most severe occupational diseases characterized by inflammatory cell infiltration, fibroblasts activation, and fibrosis in the lung. However, specific drug treatments are lacking. Cardamonin (CDM) has been reported to possess antitumor, anti-inflammatory/fibrotic effects. While, the effect of CDM on the progression of silicosis remains unknown. In this study, we established a SiO2-M stimulated fibroblast cell model, and explored the antifibrotic effect of CDM and the related molecular mechanism using WB, RT-qPCR, and immunofluorescence. The results indicate that CDM inhibits SiO2-M-induced fibroblast activation, proliferation, and migration. Furthermore, a silicosis mouse model was established through injecting silica suspension intratracheally. The results revealed that CDM retards the progression of pulmonary fibrosis. The RNA sequencing results suggest that the antifibrotic effect of CDM may be mediated by the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway. In conclusion, the results of this study demonstrate that CDM inhibits the development of silicosis via the PI3K-AKT signaling pathway, which could provide guidance for the development of drugs for silicosis treatment.

Keywords

• Silicosis
• Cardamonin
• Fibroblast
• Myofibroblast
• Macrophage
• PI3K-AKT