通过EGR1-依赖的GPX4抑制,GPR91通过EGR1-依赖的GPX4抑制调解低切割应激诱导的内皮铁
Ming Su1, Qian Wu2, Yile Zhang1
1Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
Cellular signalling
|September 12, 2025
概括
低剪压 (LSS) 在血管内皮细胞中触发了称为铁亡的编程细胞死亡. 这通过新的GPR91/EGR1/GPX4途径发生,为血管疾病提供潜在的治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 细胞死亡机制 细胞死亡机制
- 分子医学是分子医学.
背景情况:
- 低剪压 (LSS) 与内皮功能障碍和动脉样硬化有关.
- 将LSS与内皮损伤联系在一起的精确分子通路尚未完全阐明.
研究的目的:
- 为了研究LSS在诱导血管内皮细胞中的铁亡中的作用.
- 为了确定负责LSS诱导的铁亡的分子信号轴.
主要方法:
- 生物信息学和单细胞RNA测序 (scRNA-seq) 用于识别LSS响应基因.
- 平行板流室系统用于将LSS应用于人类血管内皮细胞.
- ChIP-qPCR和RNA-seq以阐明下游的信号通路.
主要成果:
- 证实LSS在内皮细胞中诱导铁亡标记物.
- 在LSS上调节了机械敏感受体GPR91.1.
- GPR91的激活导致了EGR1-介导的GPX4转录的抑制,促进了铁亡.
结论:
- 一个涉及GPR91,EGR1和GPX4的新型信号轴调解LSS诱导的血管内皮细胞中的铁亡.
- 这一途径代表了动脉样硬化和其他由改变的剪切应力驱动的血管病理的潜在治疗标.
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