长非编码RNATHAP7-AS1与EIF3A相互作用,并增强ITPR1以增强缺血性中风中的内分泌网膜应激和内皮细胞烧灭
Yini Pan1, Hui Chen1, Jianhua Xu1
1Jiading District Central Hospital Affiliated Shanghai University of Medicine &Health Sciences, Shanghai 201899, China.
Brain research bulletin
|December 27, 2025
概括
这种THAP7-AS1/EIF3A/ITPR1通路促进内皮细胞灭和ER压力在缺血性中风. 抑制这一轴可能为与中风相关的内皮损伤提供新的治疗策略.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
背景情况:
- 像THAP7-AS1这样的长非编码RNA (lncRNAs) 在细胞过程中扮演着新兴的角色.
- 在人类内皮细胞和缺血性中风中THAP7-AS1的特定功能在很大程度上是未知的.
- 内皮细胞功能障碍,热和内细胞网膜 (ER) 压力是缺血性中风病理学的关键特征.
研究的目的:
- 研究THAP7-AS1在人类静脉内皮细胞中在缺血性中风期间的功能作用.
- 阐明涉及THAP7-AS1.1.的分子相互作用和信号级联.
- 探索针对THAP7-AS1途径用于中风治疗的治疗潜力.
主要方法:
- RNA-免疫沉 (RNA-IP) 和拉下测试以识别THAP7-AS1相互作用蛋白.
- 免疫光染色以确认蛋白质-RNA联合定位.
- 氧气-葡萄糖剥夺 (OGD) 模型在体外和体内 (中风小鼠) 模拟缺血状况.
- 基因淘汰和过度表达的实验.
- 对热和ER压力标志物的评估.
- 使用Xestospongin C.进行ITPR1的药理抑制.
主要成果:
- 发现THAP7-AS1在内皮细胞中与EIF3A相互作用.
- 抑制THAP7-AS1或EIF3A降低了ITPR1的表达,并减轻了OGD诱导的热和ER压力.
- 在OGD模型中,THAP7-AS1,EIF3A和ITPR1被上调,促进内皮细胞损伤.
- 过度表达ITPR1恶化了OGD诱导的热和ER压力.
- 在体内抑制ITPR1降低了中风小鼠中的脑梗塞和烧亡标志物.
结论:
- THAP7-AS1/EIF3A/ITPR1轴是内皮细胞灭和缺血性中风中的ER应激的关键调节器.
- 这一途径在缺血性损伤后显著促进内皮细胞功能障碍.
- 针对THAP7-AS1/EIF3A/ITPR1轴是一个有希望的治疗策略,用于减轻与中风相关的内皮损伤.
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