Exosomes secreted by FNDC5-BMMSCs protect myocardial infarction by anti-inflammation and macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 axis.
Exosomes secreted by FNDC5-BMMSCs protect myocardial infarction by anti-inflammation and macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 axis.
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纤连蛋白结构域蛋白5修饰的骨髓间充质干细胞（FNDC5 - BMMSCs）分泌的外泌体通过核因子-κB（NF - κB）信号通路及核因子E2相关因子2/血红素加氧酶-1（Nrf2/HO - 1）轴发挥抗炎及调节巨噬细胞极化作用，进而对心肌梗死起到保护作用。
DOI：
10.1186/s13287-021-02591-4
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发表时间：
2021-09-28
影响因子：
7.5
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Ning H;Chen H;Deng J;Xiao C;Xu M;Shan L;Yang C;Zhang Z
外切体被认为是基于干细胞的心肌梗死(MI)治疗的替代品。FNDC5是一种位于细胞质中的跨膜蛋白，在炎症性疾病和心肌梗死修复中发挥重要作用。此外，我们先前的研究发现，FNDC5预处理的骨髓间充质干细胞(BMMSCs)可以分泌更多的外切体，但对MI的修复知之甚少。将含或不含FNDC5-OV的骨髓间充质干细胞分离的外切体注射到梗死心肌中。检测心肌细胞凋亡和炎症反应。在此基础上，将外切小体作用于RAW264.7巨噬细胞，观察其对炎症反应和巨噬细胞极化的影响。与MSCs-Exo相比，FNDC5-MSCs-Exo在体内具有更好的抗炎、抗凋亡以及M2巨噬细胞极化的治疗作用。同时，体外实验结果还表明，FNDC5-MSCs-Exo可减少脂多糖刺激下的促炎分泌，增加抗炎分泌，部分抑制了NF-κB信号通路，上调了Nrf2/HO-1轴。FNDC5-BMMSCs来源的外切体通过NF-κB信号通路和NRF2/HO-1轴发挥抗炎作用，促进M2巨噬细胞极化，有望开发一种无细胞治疗MI的方法。网上版载有补充材料，可在10.1186/s13287-021-02591-4查阅。
Exosomes are considered a substitute for stem cell-based therapy for myocardial infarction (MI). FNDC5, a transmembrane protein located in the cytoplasm, plays a crucial role in inflammation diseases and MI repair. Furthermore, our previous study found that FNDC5 pre-conditioning bone marrow-derived mesenchymal stem cells (BMMSCs) could secrete more exosomes, but little was known on MI repair. Exosomes isolated from BMMSCs with or without FNDC5-OV were injected into infarcted hearts. Then, cardiomyocytes apoptosis and inflammation responses were detected. Furthermore, exosomes were administrated to RAW264.7 macrophage with LPS treatment to investigate its effect on inflammation and macrophage polarization. Compared with MSCs-Exo, FNDC5-MSCs-Exo had superior therapeutic effects on anti-inflammation and anti-apoptosis, as well as polarizing M2 macrophage in vivo. Meanwhile, the in vitro results also showed that FNDC5-MSCs-Exo decreased pro-inflammatory secretion and increased anti-inflammatory secretion under LPS stimulation, which partly depressed NF‐κB signaling pathway and upregulated Nrf2/HO-1 Axis. FNDC5-BMMSCs-derived exosomes play anti-inflammation effects and promote M2 macrophage polarization via NF-κB signaling pathway and Nrf2/HO-1 Axis, which may develop a promising cell-free therapy for MI. The online version contains supplementary material available at 10.1186/s13287-021-02591-4.
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影响因子：
3.2
作者：
Arbab AAI;Lu X;Abdalla IM;Idris AA;Chen Z;Li M;Mao Y;Xu T;Yang Z
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Hare JM
影响因子：
37.8
作者：
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通讯作者：
Marbán E
DOI：
10.1007/s00018-016-2223-0
发表时间：
2016-09
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Loboda A;Damulewicz M;Pyza E;Jozkowicz A;Dulak J
通讯作者：
Dulak J
梗塞心脏恶劣的微环境加速移植骨髓间充质干细胞损伤：受损心肌细胞来源的外泌体的作用
影响因子：
9
作者：
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Liu S