在暴露于有毒物质后,肝脏和血液的跨组织分子反应
Bo Zhang1, Benpeng Miao2, Shuhua Fu3
1Washington University School of Med.
Research square
|November 24, 2025
概括
早期接触有毒物质可以改变表观遗传学标记. 虽然大多数分子变化是组织特异性的,但血液和肝脏的共享免疫路径和转录因子改变为环境健康研究提供了洞察力.
科学领域:
- 环境表观遗传学环境表观遗传学
- 毒理学 毒理学 毒理学
- 多个omics的多个omics.
背景情况:
- 早期接触有毒物质可以破坏表观遗传学标记,影响疾病易感性.
- 人类环境暴露研究通常使用血液作为代用组织,但有毒物质反应在器官之间有很大差异.
研究的目的:
- 为了确定代理组织 (血液) 的表观基因组变化是否反映了在早期暴露于有毒物质后,目标组织 (肝脏) 的变化.
- 为了确定在暴露于有毒物质后,组织中保存的分子反应.
主要方法:
- 系统分析来自塔吉特II联盟的1,013个多主题数据集.
- 在围产期暴露于各种有毒物质 (,,BPA,TBT,DEHP,TCDD,PM2.5) 后,对小鼠肝脏和血液中的分子反应进行比较.
主要成果:
- 大多数毒剂诱导的分子变化是肝脏和血液之间的组织特异性.
- 在这两种组织中确定了一组共同调节的基因和调节元件.
- 与免疫相关的途径和特定的转录因子 (Klf, Jun, Ets1, Cebp) 常常受到影响.
结论:
- 暴露于有毒物质后的分子变化很少在组织之间保持.
- 转录因子和生物通路的共同变化提供了一个潜在的策略,在环境表观遗传学研究中将代理组织发现与目标组织影响联系起来.
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