一个全面的转录组对人类小肠中个别核受体通路的表征
Sam Willemsen1,2,3, Fjodor A Yousef Yengej1,2, Jens Puschhof1,2,3,4
1Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, Utrecht 3584 CT, The Netherlands.
概括
核受体 (NR) 调节肠道功能. 这项研究确定了控制人类肠道器官中营养吸收,电解质平衡和药物代谢的特定NR,揭示了新的治疗点.
科学领域:
- 分子生物学分子生物学
- 胃肠病学 胃肠病学
- 药理学 药理学是指药理学的学科.
背景情况:
- 核受体 (NR) 是检测脂友化合物的转录因子,对生物调节至关重要.
- 在小肠中,NRs作为内源和外源信号的传感器,但它们的具体下游效应尚未完全理解.
研究的目的:
- 为了研究人类肠道有机体中六个核受体的单独激活.
- 描述NR激活对关键肠细胞功能的下游影响,包括营养吸收,电解质平衡和药物代谢.
主要方法:
- 利用人类肠道器官来研究六种不同的核受体 (NR).
- 管理小分子激动剂以单独激活特定的NRs.
- 进行了全面的转录基因分析,以确定基因表达和细胞功能的变化.
主要成果:
- NR激活显著改变了脂质,葡萄糖和氨基酸的吸收,电解质平衡和药物代谢.
- 确认了PXR,LXR,FXR和PPARα作为肠道脂质吸收的调节剂.
- 在小肠中复制了已知的阿里碳化合物受体 (AHR) 和维生素D受体 (VDR) 激活的肝脏效应.
- 确定了用于肠道PXR (ERG28,TMEM97,TM7SF2),LXR (RAB6B) 和VDR (CA12) 激活的新型基因.
结论:
- 这项研究提供了人类小肠中个别NR通路的综合转录基因地图.
- 这些发现突出了利用特定NR途径用于药理和治疗干预的潜力.
- 确定了独特的肠道向基因,为向药物开发提供了新的途径.
相关概念视频
01:31Transducer Mechanism: Nuclear Receptors
1.3K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.3K
01:26Signal Transduction: Overview
8.2K
Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
Typically, signal transduction involves three...
8.2K
02:24Ribosome Profiling
3.5K
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
3.5K