在实验性缺血性中风中,HuR缺陷取消了增强的NLRP3信号
Xiaojie Wang1, Mingfeng Zhao2, Xiulian Lu3
1Department of Pharmacology, School of Basic Medical Sciences, Shandong University, Jinan, China.
概括
人类抗原R (HuR) 蛋白在脑缺血/再输损伤中被上调. 沉默HuR可以减少炎症和神经元损伤,这表明HuR是中风的治疗点.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 人类抗原R (HuR) 是一种关键的RNA结合蛋白,调节mRNA命运.
- 在脑缺血/再输损伤 (CIRI) 中HuR的作用尚不清楚.
- 炎症和神经元损伤是CIRI的关键组成部分.
研究的目的:
- 调查HuR在脑缺血/再损伤 (CIRI) 中的作用.
- 阐明HuR影响CIRI的机制.
- 评估HuR作为缺血性中风的潜在治疗点.
主要方法:
- 在CIRI模型中研究了HuR表达水平.
- 在氧气-葡萄糖剥夺/再输液 (OGD/R) 治疗的细胞中使用了HuR沉默.
- 在体内研究了微质HuR缺乏的作用.
- 分析了NLRP3炎症酶激活及其通过HuR的调节.
- 使用AU丰富元素 (ARE) 分析检查了HuR和NLRP3mRNA之间的相互作用.
- 评估了NADPH氧化酶介导的ROS在HuR上调中的作用.
主要成果:
- 在CIRI之后,HuR表达显著增加.
- 沉默HuR抑制了微质炎症反应,并在OGD/R模型中减少了神经元损伤.
- 微质HuR缺乏改善了CIRI,并在体内减少了NLRP3炎症酶激活.
- 通过与其3' UTR ARE结合,HuR直接调节了NLRP3 mRNA的稳定性.
- HuR上调取决于由NADPH氧化酶衍生的活性氧物种 (ROS).
- 在实验性缺血性中风中观察到的强化NLRP3信号,HuR缺乏逆转了.
结论:
- 在CIRI期间,HuR在调节NLRP3表达和炎症酶激活方面发挥着关键作用.
- 针对HuR是一个有前途的治疗策略,用于治疗脑缺血性中风.
- 受到ROS影响的HuR-NLRP3轴是缺血性脑损伤的关键途径.
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