Work

SOX18 influences the progression of silicosis through the regulation of lymphangiogenesis

Year: 2025

Type: article

Abstract: 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 (PGE 2 ) was used to enhance the expression of SOX18, which subsequently improved tube formation and cell migration. In vivo experiments showed that PGE 2 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.

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2025.119460