环境与职业医学2026，Vol.43Issue(1)：28-34,7.DOI:10.11836/JEOM25272
巨噬细胞囊泡中补体成分1r诱导矽肺小鼠成纤维细胞活化
Macrophage-derived extracellular vesicles carrying component 1r induce fibroblast activation in silicosis mice
摘要
Abstract
[Background]Silicosis,an occupational lung disease induced by chronic silica(SiO2)exposure,is pathologically defined by progressive pulmonary fibrosis,and its associated molecular mecha-nisms are not yet fully elucidated. [Objective]To understand the critical role of macrophage-derived vesicles in silicotic pulmonary fibrosis via their carried complement component 1r(C1R). [Methods]Through integrated analysis of human plasma vesicle proteomics and spatial tran-scriptomics in silicosis mouse models,the key molecular C1R was identified in silicotic fibrosis.Spatial transcriptomic data were further employed to analyze the expression distribution of C1R in lung tissues.In animal experiments,a mouse silicosis model was established via tracheal instil-lation of silica dust,followed by pulmonary fibrosis assessed by Sirius Red staining,and C1R ex-pression levels in plasma and lung tissue vesicles examined by Western blot.In cellular experi-ments,an in vitro model was constructed by stimulating macrophages with silica.Extracellular vesicles isolated from this system were then co-cultured with mouse lung fibroblasts(MLG),followed by intervention with a C1R-neutralizing antibody. [Results]The proteomic analysis of human plasma vesicles revealed a significant upregulation of C1R in silicosis patients,confirmed by Western blot.The spatial transcriptomics in silicotic mice indicated elevated C1R expression in lung tissues after 56 d of SiO2 exposure,colocalizing with fibrotic lesions.The results of Western blot further demonstrated increased C1R levels in both lung tissue-derived and peripheral blood-derived vesicles during silicosis progression,consistent with the findings in an ex vivo macrophage model.The results of functional assays demonstrated that macrophage-derived vesicles significantly increased the expression of fibrosis markers,including fi-bronectin 1(FN1),collagen type Ⅰ alpha 1(COL1A1),and alpha-smooth muscle actin(α-SMA),as well as the migratory capacity of lung fi-broblasts;these effects were blocked by the C1R-neutralizing antibody. [Conclusion]Macrophage vesicles drive fibroblast activation and migration through C1R.Since a C1R-neutralizing antibody blocks this pro-fibrotic effect,C1R represents a key mediator in silicosis and thus is considered a new potential therapeutic target.关键词
矽肺/肺纤维化/补体C1R/细胞外囊泡/巨噬细胞/中和性抗体Key words
silicosis/pulmonary fibrosis/component 1r/extracellular vesicle/macrophage/neutralizing antibody分类
医药卫生引用本文复制引用
王子琪,成于思,沙晓娟,巢杰..巨噬细胞囊泡中补体成分1r诱导矽肺小鼠成纤维细胞活化[J].环境与职业医学,2026,43(1):28-34,7.基金项目
国家自然科学基金项目(82373547) （82373547）
