酸盐激酶M2核转移调节细胞因子风暴中与铁死相关的急性肺损伤
Haiting Wang1,2, Chenyu Fan3, Xuelian Chen4
1Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Inflammation
|March 14, 2024
概括
酸激酶M2 (PKM2) 调节细胞因子风暴诱导的急性肺损伤中的糖解和铁. 向PKM2显示出治疗患者高炎症和铁细胞死亡的潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 代谢途径 代谢途径
背景情况:
- 细胞因子风暴 (CS) 与巨细胞功能障碍和急性肺损伤 (ALI) 有关,导致死亡率.
- 糖解,由酸激酶M2 (PKM2) 调节,对于促炎性巨细胞至关重要.
- 铁亡,一种编程细胞死亡的形式,与CS相关的ALI有关,但其与糖解的联系仍然不清楚.
研究的目的:
- 调查CS诱导的ALI中糖解和铁化之间的关系.
- 探索PKM2在调节这些过程中的作用.
- 评估向PKM2.2的治疗潜力.
主要方法:
- 在使用多I:C和LPS的小鼠模型中诱导CS相关的ALI.
- 使用铁灭酶抑制剂 (费洛斯塔丁-1) 和PKM2抑制剂 (ML-265).
- 分析糖解,PKM2转位,铁亡标记物和患者样本 (CD14+单细胞).
主要成果:
- 由CS诱导的ALI表现出显著的铁亡,而铁素-1.
- 膜巨细胞显示了增强的葡萄糖分解和PKM2转位.
- ML-265治疗改善了生存率,减少了肺损伤,降低了铁亡,并重新平衡了细胞代谢.
- 在肺部感染患者中,PKM2表达与炎症相关,在单细胞中观察到增加的铁和PKM2核转位.
结论:
- PKM2 作为一个关键的调节器,在铁灭过程中整合了代谢重编程和核功能.
- 向PKM2提供了一种潜在的策略,以减轻与ferroptotic细胞死亡相关的超炎症状态和细胞因子风暴综合征.
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