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

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 SiO ₂ -induced EndoMT model and established a mouse model with pulmonary fibrosis by silica. We identified that SiO ₂ effectively increased the expression of mesenchymal markers while decreasing the levels of endothelial markers in endothelial cells. It's further demonstrated that SiO ₂ 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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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