中性粒细胞胞外陷阱
败血症
发病机制
细胞外
肺
下调和上调
体外
免疫学
炎症
体内
医学
细胞生物学
生物
基因
内科学
生物化学
生物技术
作者
Hao Zhang,Jinlong Liu,Yilu Zhou,Mengdi Qu,Yanghanzhao Wang,Kefang Guo,Ruling Shen,Zhirong Sun,Juan P. Cata,Shuofei Yang,Wankun Chen,Changhong Miao
摘要
Neutrophil extracellular traps (NETs) production is a major strategy employed by polymorphonuclear neutrophils (PMNs) to fight against microbes. NETs have been implicated in the pathogenesis of various lung injuries, although few studies have explored NETs in sepsis-associated acute lung injury (SI-ALI). Here, we demonstrate a major contribution of NETs to the pathology of sepsis-associated ALI by inducing ferroptosis of alveolar epithelial cells. Using both in vitro and in vivo studies, our findings show enhanced NETs accumulation in sepsis-associated ALI patients and mice, as well as the closely related upregulation of ferroptosis, the induction of which depends on METTL3-induced m6A modification of GPX4. Using a CLP-induced sepsis-associated ALI mouse model established with METTL3-/- versus WT mice, in addition to METTL3 knockout and overexpression in vitro, we elucidated and confirmed the critical role of ferroptosis in NETs-induced ALI. These findings support a role for NETs-induced METTL3 modification and the subsequent induction of ferroptosis in the pathogenesis of sepsis-associated ALI.
科研通智能强力驱动
Strongly Powered by AbleSci AI