网络毒理学和免疫代谢失调:将基和多基物质暴露与骨关节炎病原体产生联系起来
Qian Zhang1, Wenqi Zhang1, Zhuchen Liu1
1Department of Orthopaedics and Traumatology III, The First Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine, No. 411, Gogol Street, Nangang District, Harbin 150040, China.
Toxicology research
|June 30, 2025
概括
通过破坏免疫和代谢途径,暴露于和多基物质 (PFAS) 会使骨关节炎 (OA) 恶化. 这项研究确定了关键的遗传标,以及用于预测暴露个体中OA风险的诺姆图.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 生物信息学是一种生物信息学.
背景情况:
- 和多基基物质 (PFAS) 是广泛存在的环境污染物,具有已知的健康风险.
- 关联PFAS暴露与骨关节炎 (OA) 病变的特定分子机制尚不清楚.
研究的目的:
- 研究通过PFAS促进OA发展的分子标和途径.
- 在暴露于PFAS的人群中确定OA的潜在生物标志物和治疗标.
主要方法:
- 网络毒理学和生物信息学方法用于分析转录组数据 (GSE48556).
- 在OA中鉴定出差异表达基因 (DEGs),并与PFAS相关基因 (PSRGs) 进行交叉引用.
- 进行了蛋白质-蛋白质相互作用网络,通路丰富,免疫透分析和诺莫格拉姆构造.
主要成果:
- 在OA中共发现了1703个DEG,在DEG和PSRG之间发现了26个重叠基因.
- 关键的破坏途径包括IL-17信号传递,Th1/Th2分化和脂肪酸代谢.
- 一个五个目标的诺基图 (CARD11,IFNG,PAX8,PLD1,ZNF609) 有效地预测了OA风险,免疫分析显示了显著的T细胞和NK细胞透.
结论:
- 暴露于PFAS会通过调节免疫-炎症和代谢途径而加剧关节炎,导致突炎和软骨退化.
- 这项研究确定了新的遗传标,以及在暴露于PFAS的个体中预测OA的预测名录.
- 这项工作为OA中PFAS毒性的系统级理解提供了帮助,并建议了潜在的治疗策略.
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