在2D和3D肺上皮模型中,PFOA通过PFOA重新连接Hippo-Inflammation-Polycomb轴的ROS驱动的重新连接
M Thakur1, D Mutyala1, A A Amoliga1
1Laboratory of Pulmonary Immunotoxicology, Department of Environmental Toxicology, Southern University and A&M College, Baton Rouge, Louisiana, 70813, USA.
Toxicology
|February 7, 2026
概括
perfluorooctanoic 酸 (PFOA) 破坏肺细胞氧化还原平衡和免疫信号,导致表观遗传变化和应激反应. 这些效应即使在低度下也会发生,影响肺上皮细胞.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
背景情况:
- perfluorooctanoic 酸 (PFOA) 是一种持久性有机污染物和PFAS化学物质,具有已知的全身毒性.
- 酸对肺上皮质完整性的影响,特别是在环境相关的水平上,需要进一步研究.
研究的目的:
- 为了研究人类肺膜上皮细胞 (A549) 对PFOA暴露的细胞和分子反应.
- 探索PFOA对炎症媒介,压力反应,表观遗传修饰和信号通路的影响.
主要方法:
- 在2D和3D空气-液体接口 (ALI) 模型中培养的A549细胞被暴露在10-1000nM的PFOA中.
- 评估的促炎媒介 (NF-κB,STAT3,TLR4,RAGE,IL-6,IL-8,CCL2,CCL5),压力反应 (压力颗粒,P体),河马信号 (YAP/TAZ) 和表观遗传标记 (H3K27me3,H2AK119Ub).
- 研究了氧化应激和N-乙半氨酸 (NAC) 在调解PFOA效应中的作用.
主要成果:
- 暴露于PFOA诱导了促炎媒介释放和转化应激反应.
- PFOA激活了多胞体抑制复合体和相关的组织蛋白标记,表明表观遗传基因沉默.
- 氧化应激被确定为表观遗传和Hippo路径中断的主要驱动因素,NAC可以减轻.
- 表皮细胞迁移不受急性PFOA暴露的影响.
结论:
- 在肺上皮细胞中,PFOA破坏了氧化还原稳定,免疫信号和表观遗传可塑性.
- 确定了PFOA毒性的关键分子机制和潜在生物标志物.
- 调查结果为PFAS化学品的生物监测和监管框架提供了信息.
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