%0 Journal Article
%T FAP expression dynamics and role in silicosis: Insights from epidemiological and experimental models.
%A Deng X
%A Cheng Z
%A Li Y
%A Duan M
%A Qi J
%A Hao C
%A Yao W
%J Environ Pollut
%V 356
%N 0
%D 2024 Sep 1
%M 38838811
%F 9.988
%R 10.1016/j.envpol.2024.124311
%X 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.