通过ETS1和p38/JNK MAPK通路的铁触发信号调节Bmp6表达
Gabriela Zurawska1, Aneta Jończy1, Marta Niklewicz1
1International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland.
American journal of hematology
|January 31, 2024
概括
肝细胞中的骨形态遗传蛋白6 (BMP6) 转录受铁水平的调节. 研究人员确定了ETS1和MAP激酶信号作为关键调节器,独立于NRF2,揭示了细胞铁传感的新见解.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 铁的新陈代谢 铁的新陈代谢
背景情况:
- 骨形态基因蛋白6 (BMP6) 是一种对铁的感知细胞因子,对于调节主要的铁调节激素 - - 肝素至关重要.
- 通过铁在肝脏阴侧内皮细胞 (LSECs) 中进行BMP6转录调节的精确机制受到辩论,并提出了细胞自主信号传递 (例如NRF2) 与肝细胞的近因子之间的作用.
研究的目的:
- 阐明了对铁反应的LSECs中BMP6转录调节的分子机制.
- 研究转录因子NRF2的作用,并确定LSEC铁检测中涉及的新型调节途径.
主要方法:
- 使用具有肝细胞铁积累但没有系统过载的老年小鼠来研究BMP6调节.
- 采用光激活细胞分类 (FACS) 用于LSEC隔离和转录组分析.
- 在初级LSEC中进行了siRNA介导的淘汰,小分子治疗和染色体免疫沉试验.
主要成果:
- 来自老年小鼠的LSEC显示BMP6mRNA水平增加,而没有NRF2通路激活.
- 主要的LSEC,包括NRF2淘汰小鼠的LSEC,在暴露于铁时诱导了BMP6的表达.
- 确定ETS1是调节BMP6的关键转录因子,由p38/JNK MAP激酶信号介导,与NRF2在很大程度上独立.
结论:
- 在LSEC中,BMP6转录由铁通过ETS1和p38/JNK MAP激酶信号调节.
- 这一途径至少部分独立于NRF2介导的氧化应激反应.
- 这些发现揭示了LSEC铁感应机器与细胞应激反应相关的新型组件.
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