Exosomes from adipose-derived stem cells alleviate the inflammation and oxidative stress via regulating Nrf2/HO-1 axis in macrophages
Exosomes from adipose-derived stem cells alleviate the inflammation and oxidative stress via regulating Nrf2/HO-1 axis in macrophages
复制标题
来自脂肪干细胞的外泌体通过调节巨噬细胞中的 Nrf2/HO-1 轴减轻炎症和氧化应激
DOI：
10.1016/j.freeradbiomed.2021.01.023
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发表时间：
2021-01-29
影响因子：
7.4
通讯作者：
Hu, Dahai
中科院分区：
文献类型：
--
作者：
Shen, Kuo;Jia, Yanhui;Hu, Dahai
ADSCs exosomes作为细胞间通讯的重要手段，可以调节一系列生物学过程，包括促进组织修复和再生，以及减轻炎症。本研究发现，ADSCs exosomes可通过调节Nrf 2和HO-1的表达，使巨噬细胞向抗炎表型转化，改善脓毒症时的炎症反应和多器官损伤。我们发现，ADSCs外泌体可以减轻LPS诱导的ROS积累和炎性细胞因子IL-1？，TNF-？，和巨噬细胞中的IL-6。Western blot和流式细胞仪检测结果显示，经ADSCs exosomes预处理后，LPS刺激的巨噬细胞M1标志物（iNOS和CD 86）表达明显下降，而M2标志物（Arg 1和CD 206）表达明显增强。此外，应激相关分子HO-1在ADSC exosomes预处理后上调。进一步的H 0 -1干扰实验表明ADSCs exosomes的抗炎作用依赖于HO-1。此外，ADSC外泌体增强Nrf 2的表达和核转位，同时下调其负介质Keap 1。在体内脓毒症模型中，静脉注射ADSCs exosomes可减轻炎症细胞因子风暴和器官损伤，同时促进HO-1的表达。结论：ADSCs exosomes通过调控Nrf 2/HO-1表达减轻LPS诱导的炎症反应，对脓毒症具有保护作用。
ADSCs exosomes, an important means of intercellular communication, can regulate an array of biological pro-cesses, including promoting tissue repairs and regeneration, and attenuating inflammation. In this study, we found that ADSCs exosomes could polarize macrophage to an anti-inflammatory phenotype via regulating the expression of Nrf2 and HO-1, and improve inflammatory reaction and injury of multi-organ in sepsis. We revealed that ADSCs exosomes could alleviate LPS induced accumulation of ROS and the expression of inflam-matory cytokines IL-1?, TNF-?, and IL-6 in macrophages. Western blot and Flow cytometry results indicated that expression of M1 markers (iNOS and CD86) in LPS stimulated macrophages were significantly declined, while M2 (Arg1 and CD206) were enhanced when pretreated with ADSCs exosomes. Besides, the stress-related molecule HO-1 was upregulated when pretreated with ADSCs exosomes. Further H0-1 interference experiment indicated that anti-inflammatory effect of ADSCs exosomes was dependent on HO-1. Moreover, ADSCs exosomes enhanced expression and nucleus translocation of Nrf2, while downregulated its negative mediator Keap1. In in vivo sepsis models, intravenous injection of ADSCs exosomes relieved inflammatory cytokines storm and organ injury, while promoted expression of HO-1. In conclusion, we proved that ADSCs exosomes alleviated LPS induced inflammation and exerted protective effect in sepsis via regulating Nrf2/HO-1 expression.