SSO targets CD36 to regulate lipid metabolism disorders and improve SiO₂ induced fibrosis

Silicosis is an occupational disease caused by inhalaling free silicon dioxide (SiO₂). Lipid metabolism plays an important role in silicosis. CD36 is a key factor involved in lipid transport, but its mechanism of action in silicosis remains unclear. This study aims to explore the mechanism by which the CD36 inhibitor sulfo-n-succinimide oleate (SSO) targets CD36 to regulate lipid metabolism disorders in silicosis and improve fibrosis. The results showed that SiO₂ stimulation led to an increase in CD36 expression, a decrease in LXR and ABCA1 expression, and an increase in lipid dropper formation in rat alveolar macrophages NR8383. The SSO intervention can reverse these changes, resulting in the decrease in CD36 expression, the increase in LXR and ABCA1 expression, the reduction in IL-1β, IL-6 levels and TGF-β1 secretion. Subsequently, after stimulating primary fibroblasts with the supernatants of macrophages in each group, it was found that SSO stimulation reduced the increase of α-SMA and collagen-I induced by SiO₂ and improved the level of fibrosis. In addition, in vivo animal experiments have found that SSO intervention alleviated the levels of inflammation, lipid metabolism and fibrosis induced by SiO₂ in silicosis mice, and improved the lung function of silicosis mice. These results indicate that SSO regulates SiO₂-induced lipid metabolism disorders by targeting CD36, thereby improving SiO₂-induced fibrosis. Therefore, SSO targeting CD36 may be a new strategy for treating silica-induced silicosis injury.