在急性损伤中,STING通过NCOA4依赖的ferritinophagy促进铁亡
Lini Jin1, Binfeng Yu2, Hongju Wang1
1Department of Nephrology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, China.
Free radical biology & medicine
|August 27, 2023
概括
干扰素基因刺激器 (STING) 通过促进费里丁来驱动急性损伤 (AKI) 的铁亡. 抑制STING可能为AKI提供治疗策略.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 铁亡,一种受调节的细胞死亡形式,与急性损伤 (AKI) 病原发生有关.
- 在AKI中铁亡的精确调节机制在很大程度上是未知的.
- 干扰素基因刺激器 (STING) 是一种关键的先天性免疫媒介,越来越与脂质过氧化有关,这是铁死的一个标志.
研究的目的:
- 调查STING在缺血/反 (IR) 诱导的AKI的作用和潜在机制.
- 阐明STING如何影响损和损伤中的相关细胞过程.
主要方法:
- 利用IR诱导的AKI和体外管细胞培养的小鼠模型.
- 评估了STING表达,脂质过氧化,铁灭菌标志物 (GPX4) 和铁.
- 使用遗传缺陷,药物抑制和STING的过度表达来确定其功能影响.
主要成果:
- 在IR损伤后,管中的STING表达显著上调.
- STING 缺乏症显著降低了红外线诱导的脂质过氧化,组织损伤和功能障碍.
- STING过度表达加剧了铁亡,脂质ROS产量,并降低了GPX4,依赖于通过NCOA4相互作用诱导ferritinophagy.
结论:
- 在缺血性AKI期间,STING在促进铁亡中发挥着关键作用.
- STING促进NCOA4介导的费里丁,导致铁过载和细胞损伤.
- 向STING为管理AKI提供了潜在的治疗途径.
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