SOX18 influences the progression of silicosis through the regulation of lymphangiogenesis

Silicosis is an occupational lung disease caused by prolonged inhalation of crystalline silica dust. Studies on silicosis have revealed the presence of lymphangiogenesis in the lungs of silicosis rats. SRY-box transcription factor 18 (SOX18) is a key regulatory protein involved in the differentiation of vascular endothelial and lymphatic endothelial cells, playing a crucial role in lymphangiogenesis. However, its involvement in lymphangiogenesis associated with silicosis remains unreported. In this study, we observed that the expression of VEGFR-3 in rat lung tissues increased at one week and two weeks following silica exposure, whereas the expression of SOX18 decreased. By the fourth week, both VEGFR-3 and SOX18 expression levels were downregulated. For the first time, we directly stimulated lymphatic endothelial cells with SiO₂ to establish an in vitro model and evaluate the effects of SiO₂ on these cells. The results demonstrated that SiO₂ exposure decreased the expression of SOX18 and impaired tube formation and migration of lymphatic endothelial cells. Furthermore, prostaglandin E2 (PGE₂) was used to enhance the expression of SOX18, which subsequently improved tube formation and cell migration. In vivo experiments showed that PGE₂ treatment in silicosis mice increased the expression of SOX18 and LYVE-1 in lung tissues, while reduced the expression of α-SMA. These findings suggest that SOX18 may influence the progression of silicosis through modulation of lymphangiogenesis. The targeted regulation of SOX18 provides a new approach for investigating the mechanisms of lymphangiogenesis in silicosis.