LPS预处理MSC外泌体穿梭miR-150-5p通过Irs1下调PI3K-Akt-mTOR途径增强M2巨噬细胞极化对脓毒症起保护作用

核心信息

  • 论文英文标题: Exosome-shuttled miR-150–5p from LPS-preconditioned mesenchymal stem cells down-regulate PI3K/Akt/mTOR pathway via Irs1 to enhance M2 macrophage polarization and confer protection against sepsis
  • 期刊: Front Immunol
  • 发表年份: 2024
  • DOI: 10.3389/fimmu.2024.1397722
  • PMID/PMCID: 38957471; PMC11217356

研究概览

Therefore, this study investigated whether exosomes secreted by lipopolysaccharide (LPS)-pretreated MSCs exert superior antiseptic effects, and explored the underlying molecular mechanisms. The current findings highly suggest that exosomes derived from LPS pre-conditioned MSCs represent a promising cell-free therapeutic method and highlight miR-150-5p as a novel molecular target for regulating immune hyperactivation during sepsis.

核心发现

LPS-Exo were shown to inhibit aberrant pro-inflammatory cytokines, prevent organ damages, and improve survival rates of the septic mice to a greater extent than Exo.

In vitro, LPS-Exo significantly promoted the M2 polarization of macrophages exposed to inflammation.

miRNA sequencing and qRT-PCR analysis identified the remarkable expression of miR-150-5p in LPS-Exo compared to that in Exo, and exosomal miR-150-5p was transferred into recipient macrophages and mediated macrophage polarization.

Further investigation demonstrated that miR-150-5p targets Irs1 in recipient macrophages and subsequently modulates macrophage plasticity by down-regulating the PI3K/Akt/mTOR pathway.

研究设计

Exosomes were isolated and characterized from the supernatants of MSCs.

The therapeutic efficacy of normal exosomes (Exo) and LPS-pretreated exosomes (LPS-Exo) were evaluated in terms of survival rates, inflammatory response, and organ damage in an LPS-induced sepsis model.

Macrophages were stimulated with LPS and treated with Exo or LPS-Exo to confirm the results of the in vivo studies, and to explain the potential mechanisms.

Echo Biotech 角色

外泌体miRNA测序分析+qPCR验证

关联平台: Exoomics®

关联服务与能力: EV miRNA Profiling / Sequencing, qPCR Validation

关联产品或试剂: 无明确产品引用

参考文献

原始论文: Exosome-shuttled miR-150–5p from LPS-preconditioned mesenchymal stem cells down-regulate PI3K/Akt/mTOR pathway via Irs1 to enhance M2 macrophage polarization and confer protection against sepsis Frontiers in Immunology. 2024. DOI: 10.3389/fimmu.2024.1397722. PMID/PMCID: 38957471; PMC11217356.