一种内源性烯碳化合物受体连接体对内皮功能,转录组和蛋白组进行失调
Ying-Jie Zhao1,2, Si-Yan Zhang1, Ying-Ying Wei3
1Department of Obstetrics and Gynecology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
American journal of physiology. Cell physiology
|February 5, 2025
概括
孕前症提高了酸碳化合物受体 (AhR) 活性,其配体ITE通过破坏基因表达和蛋白质酸化来损害内皮细胞功能,提供了潜在的治疗标.
科学领域:
- 内分泌学和新陈代谢学
- 血管生物学 血管生物学
- 生殖医学 生殖医学
背景情况:
- 孕前 (PE) 与改变母亲和胎儿的血液循环有关.
- 内源性阿里碳化合物受体 (AhR) 配体可能导致PE中的内皮功能障碍.
研究的目的:
- 调查AhR配体ITE是否通过扰乱人类静脉内皮细胞 (HUVECs) 中的转录组和蛋白组来损害内皮功能.
- 评估PE和没有PE的怀孕女性血清中的AhR活性.
主要方法:
- 从PE和正常压力 (NT) 怀孕的母体和脉血清中量化AhR活性.
- 使用RT-qPCR测量HUVEC中CYP1A1/B1mRNA的血清诱导变化.
- 确定ITE对HUVEC扩散和单层完整性的影响.
- 使用RNA-seq和蛋白组学分析了HUVEC中ITE诱导的转录组和蛋白组变化.
主要成果:
- 来自PE怀孕的静脉血清在HUVEC中增加了CYP1A1mRNA,表明AhR激活升高.
- 依赖于剂量的ITE抑制了内皮增殖和降低了单层完整性.
- 在HUVEC中,ITE诱导了差异性基因表达和改变了蛋白质酸化,并观察到性别特异性的影响.
- 失调的基因和蛋白在与心血管,肝脏和脏疾病以及炎症反应相关的途径中得到了丰富.
结论:
- 像ITE这样的内源性AhR配体可以通过扰乱细胞转录组和蛋白组来损害内皮功能.
- 由ITE失调的基因和蛋白代表了PE诱导的内皮功能障碍的潜在治疗标.
- AhR配体对内皮细胞的细胞性别特异性影响需要在PE的背景下进行进一步的研究.
关键词:
这是一种AhR连接体.它们是内皮细胞的内皮细胞.基蛋白质组 (Phosphoproteome) 是一种基蛋白质组.性二重形性质性质二重形性质.转录组 (transcriptome) 是一个转录组.更多相关视频
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