细胞外囊泡蛋白质组学表达受前铀矿矿工采矿权保有情况的影响。

Extracellular vesicle proteomic expression is influenced by mining tenure in former uranium miners.

作者信息

Oh Mijung, Lim Eunju, Edeh Onamma, Yazzie Sydnee, Kanda Deborah, Luo Li, Jacquez Quiteria, Jiang Ting, Adsul Prajakta, Weick Jason, Sood Akshay, Zychowski Katherine E

机构信息

Department of Pathology, School of Medicine, University of New Mexico, Albuquerque, NM, 87131, USA.

Department of Internal Medicine, School of Medicine, University of New Mexico, Albuquerque, NM, 87131, USA.

出版信息

Environ Res. 2025 Aug 31;286(Pt 1):122737. doi: 10.1016/j.envres.2025.122737.

DOI:10.1016/j.envres.2025.122737

PMID:40897222

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12457906/

Abstract

BACKGROUND

Chronic exposure to uranium (U) rich environments poses significant health risks, yet the molecular mechanisms underlying these effects remain poorly understood. Extracellular vesicles (EVs) are membrane-bound vesicles that transfer multiple biomolecules between cells and can regulate cellular function.

OBJECTIVE

To determine whether U-mining tenure is associated with specific alterations in serum-derived EV proteomic and plasma cytokine profiles among former U-miners, and to assess the potential of EV-derived proteins as robust biomarkers of chronic U-exposure relative to canonical cytokines.

METHODS

Serum and plasma samples were obtained from 39 former U-miners. Small and large EVs were isolated via differential ultracentrifugation and characterized by nanoparticle tracking and western blotting. EV proteomic profiles were analyzed using liquid chromatography-tandem mass spectrometry. Plasma cytokines were quantified using multiplex immunoassays. Age-adjusted linear regression was used to assess associations with mining tenure, and pathway enrichment analysis was performed on significant EV proteins.

RESULTS

Eight small-EV and four large-EV proteins significantly correlated with mining tenure after age adjustment. Notably, Complement C1r subcomponent and Vitamin K-dependent protein S, and Fibrinogen alpha chain exhibited strong inverse correlations. Enrichment analyses highlighted immune-related and extracellular matrix pathways. Six cytokines were initially associated with mining tenure but lost significance after age adjustment. In contrast, EV protein associations appeared more robust for this confounding, underscoring their potential as exposure biomarkers.

CONCLUSIONS

Serum EV-derived protein signatures were nominally associated with U-mining tenure independent of age, whereas cytokine profiles were confounded by age. These findings suggest that EV-derived proteins may provide sensitive biomarkers for monitoring long-term health effects of U-exposure, which warrants further investigation in larger cohorts.

摘要

背景

长期暴露于富含铀（U）的环境中会带来重大健康风险，但这些影响背后的分子机制仍知之甚少。细胞外囊泡（EVs）是膜结合囊泡，可在细胞间传递多种生物分子并调节细胞功能。

目的

确定铀矿开采年限是否与前铀矿工人血清来源的细胞外囊泡蛋白质组和血浆细胞因子谱的特定改变有关，并评估细胞外囊泡衍生蛋白相对于经典细胞因子作为慢性铀暴露可靠生物标志物的潜力。

方法

从39名前铀矿工人中获取血清和血浆样本。通过差速超速离心分离小细胞外囊泡和大细胞外囊泡，并通过纳米颗粒追踪和蛋白质印迹进行表征。使用液相色谱 - 串联质谱分析细胞外囊泡蛋白质组谱。使用多重免疫测定法定量血浆细胞因子。采用年龄调整线性回归评估与采矿年限的关联，并对显著的细胞外囊泡蛋白进行通路富集分析。

结果

年龄调整后，8种小细胞外囊泡蛋白和4种大细胞外囊泡蛋白与采矿年限显著相关。值得注意的是，补体C1r亚成分、维生素K依赖性蛋白S和纤维蛋白原α链呈现出强烈的负相关。富集分析突出了免疫相关和细胞外基质通路。6种细胞因子最初与采矿年限相关，但在年龄调整后失去显著性。相比之下，细胞外囊泡蛋白的关联在这种混杂因素下显得更为稳健，突出了它们作为暴露生物标志物的潜力。