Deng Wei, Zhu Xiaoping, Li Hang, Hu Ping, Qian Kejian, Liu Fen
Department of Critical Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China.
Medical Innovation Center, First Affiliated Hospital of Nanchang University, Nanchang, People's Republic of China.
Int J Nanomedicine. 2025 Apr 15;20:4831-4848. doi: 10.2147/IJN.S510241. eCollection 2025.
Emerging evidence links macrophage overactivation to sepsis-associated acute lung injury (ALI), yet the role of lung tissue-derived extracellular vesicles (Ti-EVs) in this process remains unclear. This study combines transcriptomic profiling and functional validation to reveal how Lung Ti-EVs mediate macrophage polarization through miRNA-dependent NLRP3 inflammasome activation.
We established a sepsis mouse model, extracted and characterized lung tissue-derived EVs, performed high-throughput transcriptome sequencing and bioinformatics analysis. Intratracheal administration of these EVs to wild-type C57BL/6 mice revealed their effects on pulmonary inflammation, macrophage polarization, and proliferation. In vitro co-culture experiments with Raw264.7 macrophages further validated these findings and explored underlying mechanisms.
We identified extracellular vesicles (EVs) enriched in lung tissues from septic ALI mice, selectively carrying miRNAs including miR-128-3p. In vivo administration of these EVs exacerbated pulmonary inflammation by expanding M1 macrophage populations, while in vitro experiments demonstrated EV-mediated miR-128-3p delivery to macrophages stimulated TNF-α and IL-6 production. Mechanistically, miR-128-3p promoted macrophage proliferation and inflammatory responses by targeting Rab20.
新出现的证据表明巨噬细胞过度激活与脓毒症相关的急性肺损伤（ALI）有关，但肺组织衍生的细胞外囊泡（Ti-EVs）在此过程中的作用仍不清楚。本研究结合转录组分析和功能验证，以揭示肺Ti-EVs如何通过miRNA依赖的NLRP3炎性小体激活介导巨噬细胞极化。
我们建立了脓毒症小鼠模型，提取并鉴定了肺组织衍生的细胞外囊泡，进行了高通量转录组测序和生物信息学分析。将这些细胞外囊泡经气管内给予野生型C57BL/6小鼠，揭示了它们对肺部炎症、巨噬细胞极化和增殖的影响。与Raw264.7巨噬细胞进行体外共培养实验进一步验证了这些发现并探索了潜在机制。
我们鉴定出脓毒症ALI小鼠肺组织中富集的细胞外囊泡（EVs），其选择性携带包括miR-128-3p在内的miRNA。在体内给予这些细胞外囊泡通过扩大M1巨噬细胞群体加剧了肺部炎症，而体外实验表明细胞外囊泡介导的miR-128-3p传递至巨噬细胞刺激了TNF-α和IL-6的产生。从机制上讲，miR-128-3p通过靶向Rab20促进巨噬细胞增殖和炎症反应。
