Silicosis is a fibrotic disease caused by long-term inhalation of SiO2 particles that currently has no effective treatment. Earlier studies have suggested that pulmonary lymphatic vessels play a key role in the transport of silica but have not address the long-term effects of altered pulmonary lymphatic drainage on silicosis. Here, we investigated the impact of impaired pulmonary lymphatic drainage on silicosis. In the past, lymphatic drainage disorders were established mainly through the use of VEGF inhibitors. For the first time, we established a model of pulmonary lymphatic drainage disorder by ligating the thoracic duct in rats. Impaired pulmonary lymphatic drainage was found to aggravate inflammation and oxidative damage in silicosis rats and accelerate silicosis progression. Next, we investigated the effect of pulmonary lymphatic drainage on silicosis. We have demonstrated the effect of sodium tanshinone IIA sulfonate(STS) on lymphangiogenesis, which revealed that STS promotes lymphangiogenesis and can delay inflammation, oxidative damage, and fibrosis progression in silicosis rats by promoting the pulmonary lymphatic drainage response, and this effect is mediated by the VEGFR-3/PI3K/AKT signaling pathway. These findings suggest that pulmonary lymphogenesis plays an important role in silicosis pathogenesis, and targeted intervention in pulmonary lymphangiogenesis may be a potential strategy for treating of silicosis in the future.
Keywords: Ligating the thoracic duct; Lymphangiogenesis; Pulmonary lymphatic drainage; Silicosis; VEGFR-3/PI3K/AKT pathway.
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