Extracellular vesicles (EVs) from adipose tissue-derived stem cells have been reported to attenuate lipopolysaccharide (LPS) induced inflammation and sepsis while the specific mechanism is unclear. This study explored the underlying molecular mechanisms of EVs from adipose tissue-derived stem cells in reducing inflammation. LPS- induced macrophage models and mice model were established to mimic inflammation in vitro and in vivo. EVs were extracted from adipose tissue-derived stem cells and identified. It was found that proinflammatory cytokines, including IL-1β, IL-6, and TNF-α, substantially decreased after EVs were applied to LPS-stimulated macrophages and mice, and thus, LPS induced M1 polarization was inhibited and sepsis was strongly alleviated. In the LPS induced macrophages, the expression of Notch signaling molecules and the activation of the NF-κB pathway were substantially decreased after the administration of EVs. Then, RBP-J^−/− mice and macrophages were used. It was found that the miR-148a-3p level was significantly lower in the RBP-J^−/− macrophages than in the wildtype macrophages. In the LPS induced macrophages, the increasing of miR-148a-3p was milder in the RBP-J^−/− macrophages than in the wild type macrophages. Then, miR-148a-3p was overexpressed in macrophages and mice, and we found that the expression of proinflammatory cytokines was increased both in vivo and in vitro. The protective effect of EVs in LPS induced sepsis was diminished by the overexpression of miR-148a-3p. In conclusion, we proved that EVs could attenuate inflammation and further protect organ function by regulating the Notch-miR148a-3p signaling axis and then decreasing macrophage polarization to M1.

据报道，来自脂肪组织干细胞的细胞外囊泡（EVs）可减轻脂多糖（LPS）引起的炎症和败血症，但具体机制尚不清楚。这项研究探索了来自脂肪组织干细胞的EV减少炎症的潜在分子机制。建立LPS诱导的巨噬细胞模型和小鼠模型以模拟炎症体外 和 体内。从脂肪组织干细胞中提取电动汽车并进行鉴定。已经发现，将EVs应用于LPS刺激的巨噬细胞和小鼠后，包括IL-1β，IL-6和TNF-α在内的促炎细胞因子显着降低，因此，LPS诱导的M1极化被抑制并且脓毒症得到了强烈缓解。在LPS诱导的巨噬细胞中，在施用EV后，Notch信号分子的表达和NF-κB途径的激活显着降低。然后，RBP-J^{- / -}中使用的小鼠和巨噬细胞。结果发现，miR-148a-3p水平明显低于正常人。RBP-J^-/-巨噬细胞比野生型巨噬细胞大。在LPS诱导的巨噬细胞中，miR-148a-3p的增加在小鼠体内较温和。RBP-J^-/-巨噬细胞比野生型巨噬细胞大。然后，miR-148a-3p在巨噬细胞和小鼠中过表达，我们发现促炎细胞因子的表达均增加体内 和 体外。miR-148a-3p的过表达减弱了EV在LPS诱导的败血症中的保护作用。总之，我们证明了电动汽车可以通过调节Notch-miR148a-3p信号轴，然后将巨噬细胞极化降低至M1来减轻炎症并进一步保护器官功能。