通过RIG-I/c-Myc/FTH轴重新编程铁代谢减轻脏缺血-再输血损伤
Yulu Zhang1, Jia Xing1, Li Yao2,3
1Department of Histology and Embryology, Basic Medical College, China Medical University, Shenyang, China.
Antioxidants & redox signaling
|August 22, 2025
概括
急性损伤涉及铁代谢的破坏. 网红酸诱导基因-I (RIG-I) 激活c-Myc,促进铁素重链 (FTH) 和铁死. 抑制c-Myc可以防止损伤.
科学领域:
- 肝脏病学
- 分子生物学
- 生物化学
背景情况:
- 急性缺血再输损伤 (IRI) 与严重的铁代谢障碍有关.
- 在IRI中这些铁破坏的确切分子机制仍然很大程度上是未知的.
研究的目的:
- 阐明铁代谢障碍与急性脏IRI相关的分子机制.
- 研究可诱导视网酸基因-I (RIG-I),c-Myc和铁素重链 (FTH) 在IRI病变发生中的作用.
主要方法:
- 针对病理性变化,铁代谢标志物和蛋白质表达 (RIG-I,c-Myc,FTH,GPX4) 的小鼠的分析.
- 使用管细胞进行体外研究以评估RIG- I,c- Myc和FTH相互作用.
- 染色体免疫沉测定和siRNA实验以确认c-Myc对FTH的调节.
- 在IRI模型中使用c- Myc抑制剂 (10058- F4) 治疗和诱导铁的疾病.
主要成果:
- IRI脏表现出病理变化,铁代谢中断,GPX4减少和铁亡的迹象.
- 在管状上皮细胞中发现了高的RIG-I,c-Myc和FTH;RIG-I促进了c-Myc的激活,这反过来又提高了FTH.
- 过度表达FTH导致RIG-I和其他与铁相关的蛋白质增加.
- 抑制c- Myc可以逆转IRI引起的损伤,改善功能和形态,平衡铁的平衡,并减少氧化应激和炎症.
结论:
- RIG-I-c-Myc-FTH轴破坏铁的稳态,并有助于IRI中的铁.
- 通过稳定铁代谢和减轻氧化应激,抑制c- Myc具有保护作用.
- 针对c- Myc途径是急性脏IRI的潜在治疗策略.
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