Micro electrical fields induced MSC-sEVs attenuate neuronal cell apoptosis by activating autophagy via lncRNA MALAT1/miR-22-3p/SIRT1/AMPK axis in spinal cord injury.
Micro electrical fields induced MSC-sEVs attenuate neuronal cell apoptosis by activating autophagy via lncRNA MALAT1/miR-22-3p/SIRT1/AMPK axis in spinal cord injury.
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DOI：
10.1186/s12951-023-02217-2
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发表时间：
2023-11-27
影响因子：
10.2
通讯作者：
Fu, Qiang
中科院分区：
文献类型：
--
作者：
Li, Kewei;Liu, Zhong;Wu, Peipei;Chen, Shenyuan;Wang, Min;Liu, Wenhui;Zhang, Leilei;Guo, Song;Liu, Yanbin;Liu, Pengcheng;Zhang, Beiting;Tao, Lin;Ding, Hua;Qian, Hui;Fu, Qiang
关键词：
脊髓损伤（SCI）是一种中枢神经系统的创伤性疾病，可导致四肢瘫痪。微电场（EF）已被用于神经损伤修复和再生的新治疗方法，但微电场（EF-sEVs）刺激诱导的人脐带间充质干细胞衍生的小细胞外囊泡对SCI的影响仍然未知。本研究的目的是研究EF-sEV是否对SCI大鼠模型具有治疗作用。收集EF-sEVs和正常条件下的人脐带间充质干细胞来源的小细胞外囊泡（CON-sEVs），并将其注射到SCI模型大鼠中以评价治疗效果。我们检测了EF-sEV和CON-sEV中候选长非编码RNA转移相关肺腺癌转录本1（lncRNA-MALAT 1）的表达。使用荧光素酶报告基因测定研究lncRNA-MALAT 1的靶标和下游效应物。使用体内和体外实验，我们证明EF-sEVs增加了SCI后的自噬并减少了凋亡，这促进了运动功能的恢复。我们进一步证实了EF-sEV在体外和体内的神经保护作用与sEV中包封的lncRNA-MALAT 1的存在相关。lncRNA-MALAT 1通过海绵作用靶向miR-22- 3 p，降低miR-22- 3 p对其靶点SIRT 1的抑制作用，这转化为AMPK磷酸化并增加抗凋亡蛋白Bcl-2的水平。总的来说，本研究确定EF-sEV中的lncRNA-MALAT 1通过miRNA-22- 3 p/SIRT 1/AMPK轴发挥神经保护作用，并提供了使用sEV改善SCI的新观点和潜在治疗方法。在线版本包含补充材料，可通过10.1186/s12951-023-02217-2获得。
Spinal cord injury (SCI) is a traumatic condition of the central nervous system that causes paralysis of the limbs. Micro electric fields (EF) have been implicated in a novel therapeutic approach for nerve injury repair and regeneration, but the effects of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles that are induced by micro electric fields (EF-sEVs) stimulation on SCI remain unknown. The aim of the present study was to investigate whether EF-sEVs have therapeutic effects a rat model of SCI. EF-sEVs and normally conditioned human umbilical cord mesenchymal stem cells-derived small extracellular vesicles (CON-sEVs) were collected and injected intralesionally into SCI model rats to evaluate the therapeutic effects. We detect the expression of candidate long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA-MALAT1) in EF-sEVs and CON-sEVs. The targets and downstream effectors of lncRNA-MALAT1 were investigated using luciferase reporter assays. Using both in vivo and in vitro experiments, we demonstrated that EF-sEVs increased autophagy and decreased apoptosis after SCI, which promoted the recovery of motor function. We further confirmed that the neuroprotective effects of EF-sEVs in vitro and in vivo correlated with the presence of encapsulated lncRNA-MALAT1 in sEVs. lncRNA-MALAT1 targeted miR-22-3p via sponging, reducing miR-22-3p’s suppressive effects on its target, SIRT1, and this translated into AMPK phosphorylation and increased levels of the antiapoptotic protein Bcl-2. Collectively, the present study identified that the lncRNA-MALAT1 in EF-sEVs plays a neuroprotective role via the miRNA-22-3p/SIRT1/AMPK axis and offers a fresh perspective and a potential therapeutic approach using sEVs to improve SCI. The online version contains supplementary material available at 10.1186/s12951-023-02217-2.
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DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
脊髓损伤：病理生理学，多分子相互作用和潜在的恢复机制。
影响因子：
5.6
作者：
Anjum A;Yazid MD;Fauzi Daud M;Idris J;Ng AMH;Selvi Naicker A;Ismail OHR;Athi Kumar RK;Lokanathan Y
通讯作者：
Lokanathan Y
影响因子：
4.3
作者：
Liu, Yubao;Lin, Lupan;Lin, Fuqing
通讯作者：
Lin, Fuqing
影响因子：
10.7
作者：
Lee, Chien-Wei;Chen, Yi-Fan;Hsiao, Allen Wei-Ting;Wang, Amanda Yu-Fan;Shen, Oscar Yuan-Jie;Wang, Belle Yu-Hsuan;Ho, Lok Wai Cola;Lin, Wei-Ting;Choi, Chung Hang Jonathan;Lee, Oscar Kuang-Sheng
通讯作者：
Lee, Oscar Kuang-Sheng
影响因子：
5.5
作者：
Liao HY;Wang ZQ;Ran R;Zhou KS;Ma CW;Zhang HH
通讯作者：
Zhang HH