Abstract：
Prolonged exposure to free silica leads to the development of silicosis, wherein activated fibroblasts play a pivotal role in its pathogenesis and progression. Fibroblast Activation Protein (FAP), as a biomarker for activated fibroblasts, its expression pattern and role in key aspects of silicosis pathogenesis remain unclear. This study elucidated the expression pattern and function of FAP through population-based epidemiological investigations, establishment of mouse models of silicosis, and in vitro cellular models. Results indicated a significant elevation of FAP in plasma from silicosis patients and lung tissues from mouse models of silicosis. In the cellular model, we observed a sharp increase in FAP expression early in the differentiation process, which remained high expression. Inhibition of FAP suppressed fibroblast differentiation, while overexpression of FAP produced the opposite effect. Moreover, fibroblast-derived FAP can alter the phenotype and function of neighboring macrophages. In summary, we revealed a high expression pattern of FAP in silicosis and its potential mechanistic role in fibrosis, suggesting FAP as a potential therapeutic target for silicosis.
摘要：
长时间接触游离二氧化硅会导致矽肺的发展，其中活化的成纤维细胞在其发病机理和进展中起关键作用。成纤维细胞活化蛋白(FAP),作为激活的成纤维细胞的生物标志物，其表达模式和在矽肺发病关键方面的作用尚不清楚。本研究通过基于人群的流行病学调查阐明了FAP的表达模式和功能。矽肺小鼠模型的建立，和体外细胞模型。结果表明，矽肺患者血浆和矽肺小鼠模型肺组织中的FAP显着升高。在细胞模型中,我们观察到FAP表达在分化过程早期急剧增加，保持高表达。抑制FAP抑制成纤维细胞分化，而FAP的过表达产生相反的效果。此外，成纤维细胞来源的FAP可以改变邻近巨噬细胞的表型和功能。总之,我们揭示了FAP在矽肺中的高表达模式及其在纤维化中的潜在机制作用，提示FAP是矽肺的潜在治疗靶点。
