相关实验视频
Updated: Jul 12, 2025

10:06
Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
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通过HNF4alpha调节肝脏外传感器功能
bioRxiv : the preprint server for biology
|October 24, 2023
概括
肝细胞核因子4alpha (HNF4α) 对于关键的外源生物传感器的功能至关重要 构成性安德罗斯坦受体 (CAR),Pregnane X受体 (PXR) 和 Peroxisome Proliferator-Activated Receptor-alpha (PPARα),影响毒理反应.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 分子毒理学分子毒理学
- 核接收器信号传输 核接收器信号传输
背景情况:
- 核受体,如阿利碳化合物受体 (AhR),构成性安德罗斯坦受体 (CAR),Pregnane X受体 (PXR) 和Peroxisome Proliferator-Activated Receptor-alpha (PPARα) 是重要的异生物传感器.
- 肝细胞核因子4alpha (HNF4α) 是肝功能必不可少的孤儿核受体.
研究的目的:
- 研究HNF4α在四个主要肝脏异生物传感器 (AhR,CAR,PXR,PPARα) 的功能激活中的重要作用.
主要方法:
- 使用了野生型 (WT) 和肝细胞特异性HNF4α淘汰 (HNF4α-KO) 的小鼠.
- 对AhR (TCDD),CAR (TCPOBOP),PXR (PCN) 和PPARα (WY-14643) 进行的特定激动剂.
- 分析了肝对体重量比和基因表达,以评估核受体激活.
主要成果:
- HNF4α-KO小鼠显示CAR,PXR和PPARα的激活中断,由受损的目标基因诱导和改变的肝对身体体重比率证明.
- 在HNF4α-KO小鼠中,TCDD对AhR的激活不受影响.
- CAR,PXR和PPARα激动剂治疗显著增加了WT小鼠的肝对体重量比和基因表达,但不是HNF4α-KO小鼠.
结论:
- HNF4α对于肝脏CAR,PXR和PPARα的功能激活至关重要.
- 对于AhR激活,HNF4α不是必不可少的.
- 这些发现凸显了HNF4α在调解肝脏异生物传感器功能和随后的毒理反应方面不可或缺的作用.
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