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Astrocyte-neuron crosstalk through extracellular vesicle-shuttled miRNA-382-5p promotes traumatic brain injury

文献类型：期刊论文

作者Hu, Qing9; Wu, Xun9; Guo, Chengxuan9; Wang, Tinghao9; Guo, Hao8,9; Wang, Jin2,9; Wang, Bodong7; Cui, Wenxing9; Bai, Hao9; Zhou, Jinpeng8,9
刊名EXPERIMENTAL AND MOLECULAR MEDICINE
出版日期2024-12-01
卷号56期号:12页码:2642-2658
ISSN号1226-3613
DOI10.1038/s12276-024-01355-3
通讯作者Qu, Yan(yanqu0123@fmmu.edu.cn) ; Feng, Jing(fengjing@simm.ac.cn) ; Liu, Haixiao(lhxiao@fmmu.edu.cn)
英文摘要Although astrocytes undergo functional changes in response to brain injury and may be the driving force of subsequent neuronal death, the underlying mechanisms remain incompletely elucidated. Here, we showed that extracellular vesicle (EV)-shuttled miRNA-382-5p may serve as a biomarker for the severity of traumatic brain injury (TBI), as the circulating EV-miRNA-382-5p level was significantly increased in both human patients and TBI model mice. Mechanistically, astrocyte-derived EVs delivered the shuttled miRNA-382-5p to mediate astrocyte-neuron communication, which promoted neuronal mitochondrial dysfunction by inhibiting the expression of optic atrophy-1 (OPA1). Consistent with these findings, genetic ablation of neuronal OPA1 exacerbated mitochondrial damage and neuronal apoptosis in response to TBI. Moreover, engineered RVG-miRNA-382-5p inhibitor-EVs, which can selectively deliver a miRNA-382-5p inhibitor to neurons, significantly attenuated mitochondrial damage and improved neurological function after TBI. Taken together, our data suggest that EV-shuttled miRNA-382-5p may be a critical mediator of astrocyte-induced neurotoxicity under pathological conditions and that targeting miRNA-382-5p-OPA1 signaling has potential for clinical translation in the treatment of traumatic brain injury. Traumatic brain injury often results in long-term disabilities. This study investigates how astrocytes contribute to nerve cell damage after TBI, focusing on extracellular vesicles and microRNAs, specifically miRNA-382-5p. The research involved blood samples from TBI patients and healthy people, and mouse experiments, to study the effects of astrocyte-derived EVs carrying miRNA-382-5p on nerve cells. The study found that after TBI, astrocytes release EVs with miRNA-382-5p, which disrupts mitochondrial function in nerve cells, causing damage. The study concludes that astrocyte-derived EVs carrying miRNA-382-5p significantly contribute to nerve cell damage after TBI. By inhibiting miRNA-382-5p, such damage can be reduced, offering a new TBI treatment approach. This research enhances our understanding of TBI and offers potential for targeted therapies. Future implications include using miRNA-382-5p as a diagnostic tool or treatment target to improve TBI outcomes. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
WOS关键词MITOCHONDRIA ; EXOSOMES ; CELLS
资助项目the National Natural Science Foundation of China (82101379)[82101379] ; the National Natural Science Foundation of China (82101379)[82130038] ; the National Natural Science Foundation of China (82101379)[32241003] ; the National Natural Science Foundation of China (82101379)[82171214] ; National Natural Science Foundation of China[23ZR1474500] ; Shanghai Municipal Natural Science Foundation[LG-QS-202203-07] ; State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences[TMKF2024B01] ; Research Project of Yunnan Key Laboratory of Gastrodia
WOS研究方向Biochemistry & Molecular Biology ; Research & Experimental Medicine
语种英语
WOS记录号WOS:001367355100001
出版者SPRINGERNATURE
源URL[http://119.78.100.183/handle/2S10ELR8/314792]  
专题中国科学院上海药物研究所
通讯作者Qu, Yan; Feng, Jing; Liu, Haixiao
作者单位1.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai, Shandong, Peoples R China
2.Zhejiang Prov Peoples Hosp, Dept Neurosurg, Hangzhou, Zhejiang, Peoples R China
3.Fourth Mil Med Univ, Dept Biomed Engn, Xian, Shaanxi, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai, Peoples R China
6.Tangdu Hosp, Dept Tradit Chinese Med, Xian, Shaanxi, Peoples R China
7.960th Hosp PLA Joint Logist Support Force, Dept Neurosurg, Jinan, Shandong, Peoples R China
8.Shaanxi Clin Res Ctr Neurosurg Dis, Xian, Shaanxi, Peoples R China
9.Tangdu Hosp, Dept Neurosurg, Xian, Shaanxi, Peoples R China
10.Univ Chinese Acad Sci, Beijing, Peoples R China
推荐引用方式
GB/T 7714		 Hu, Qing,Wu, Xun,Guo, Chengxuan,et al. Astrocyte-neuron crosstalk through extracellular vesicle-shuttled miRNA-382-5p promotes traumatic brain injury[J]. EXPERIMENTAL AND MOLECULAR MEDICINE,2024,56(12):2642-2658.
APA Hu, Qing.,Wu, Xun.,Guo, Chengxuan.,Wang, Tinghao.,Guo, Hao.,...&Liu, Haixiao.(2024).Astrocyte-neuron crosstalk through extracellular vesicle-shuttled miRNA-382-5p promotes traumatic brain injury.EXPERIMENTAL AND MOLECULAR MEDICINE,56(12),2642-2658.
MLA Hu, Qing,et al."Astrocyte-neuron crosstalk through extracellular vesicle-shuttled miRNA-382-5p promotes traumatic brain injury".EXPERIMENTAL AND MOLECULAR MEDICINE 56.12(2024):2642-2658.

入库方式： OAI收割

来源：上海药物研究所

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