LGALS3 regulates endothelial-to-mesenchymal transition via PI3K/AKT signaling pathway in silica-induced pulmonary fibrosis

• Published in: Toxicology (Amsterdam) 2024-12, Vol.509, p.153962, Article 153962
• Main Authors: Cheng, Demin, Lian, Wenxiu, Jia, Xinying, Wang, Ting, Sun, Wenqing, Liu, Yi, Ni, Chunhui
• Format: Article
• Language: English
• Subjects: Animals; Disease Models, Animal; EndoMT; Epithelial-Mesenchymal Transition - drug effects; Galectin 3 - metabolism; Humans; LGALS3; Male; Mice; Mice, Inbred C57BL; Phosphatidylinositol 3-Kinases - metabolism; PI3K/AKT; Proto-Oncogene Proteins c-akt - metabolism; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - metabolism; Pulmonary Fibrosis - pathology; Signal Transduction - drug effects; Silicon Dioxide - toxicity; Silicosis; Silicosis - metabolism; Silicosis - pathology
• ISSN: 0300-483X; 1879-3185; 1879-3185
• DOI: 10.1016/j.tox.2024.153962

Silicosis is a progressive and chronic occupational lung disease characterized by lung inflammation, silicotic nodule formation, and diffuse pulmonary fibrosis. Emerging evidence indicates that endothelial-mesenchymal transition (EndoMT) plays a crucial role in the development of silicosis. Herein, we conducted a SiO2-induced EndoMT model and established a mouse model with pulmonary fibrosis by silica. We identified that SiO2 effectively increased the expression of mesenchymal markers while decreasing the levels of endothelial markers in endothelial cells. It’s further demonstrated that SiO2 induced the PI3K/Akt signaling pathway activation via LGALS3 synthesis. Next, interfering LGALS3 blocked the process of EndoMT by inhibiting the activity of PI3K/AKT signaling. In vivo, the administration of a specific PI3K inhibitor LY294002 significantly alleviated silica-induced pulmonary fibrosis. Collectively, these results identified that the LGALS3/PI3K/AKT pathway provided a rationale target for the clinical treatment and intervention of silicosis.