肝脏HDAC3通过河马信号通路调节系统性铁平衡和铁
Hongen Meng1, Yingying Yu1, Enjun Xie1
1The Second Affiliated Hospital, The First Affiliated Hospital, Institute of Translational Medicine, School of Public Health, Zhejiang University School of Medicine, Hangzhou, China.
Research (Washington, D.C.)
|November 30, 2023
概括
希斯脱乙酶3 (HDAC3) 通过Hippo-Yap通路调节铁代谢和铁. 抑制HDAC3在铁过载条件下会影响肝素水平和肝损伤.
科学领域:
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 基因组脱乙酶 (HDACs) 是关键的表观遗传调节剂,影响细胞命运和平衡.
- HDACs在铁代谢和铁,一种依赖铁的细胞死亡中的作用尚不清楚.
研究的目的:
- 调查肝脏HDACs在调节铁代谢和铁亡中的作用.
- 阐明HDACs控制铁稳态和细胞死亡的分子机制.
主要方法:
- 使用了基因小鼠模型,特别是肝脏特异性Hdac3淘汰 (Hdac3-LKO) 的小鼠.
- 采用了转录概况,Hippo通路抑制剂,Yap过度表达和促进者记者测试.
- 分析了hepcidin mRNA水平,铁平衡,Yap核转位和ferroptosis诱导的肝损伤.
主要成果:
- Hdac3-LKO小鼠显示肝脏的Hamp mRNA (hepcidin) 减少,铁的稳定性也发生变化.
- 鉴定出Hippo-Yap通路是Hdac3的下游,Yap激活导致Hamp mRNA的减少.
- HDAC3抑制促进了雅普核转位,构成性活跃的雅普模仿了Hdac3-LKO表型.
- 铁过载导致的铁死导致Hdac3-LKO小鼠的肝损伤,这种损伤通过Yap敲击得到改善.
结论:
- 通过Hippo-Yap信号通路,HDAC3在表观遗传上调节铁的稳态和铁.
- 抑制HDAC3会影响肝素的表达,并在铁过载时加剧与ferroptosis相关的肝损伤.
- HDAC3和Hippo-Yap通路代表了管理与铁过载相关的疾病和铁的潜在治疗点.
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