神经干细胞来源的外泌体FTO通过抑制小胶质细胞NRF2 mRNA m6A修饰来保护神经元免受小胶质细胞炎症损伤。

IF 1.8 4区 医学 Q3 GENETICS & HEREDITY Journal of neurogenetics Pub Date : 2023-09-01 Epub Date: 2023-10-16 DOI:10.1080/01677063.2023.2259995
Zhiyong Li, Zhenggang Chen, Jun Peng
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引用次数: 0

摘要

缺血性中风(IS)可导致神经元细胞损失和功能缺陷。来源于神经干细胞的外泌体(NSC-Exos)改善IS后的神经可塑性并促进神经功能修复。然而,其潜在机制尚不清楚。本研究对NSC外显子进行了表征,并与小胶质细胞共培养。我们发现NSC-Exos在氧-葡萄糖剥夺/复氧和LPS诱导的小胶质细胞中增加了NRF2的表达,并将小胶质细胞从M1促炎表型转化为M2抗炎表型。NSC-Exos通过肥胖相关基因(FTO)减少核因子红系2相关因子2(NRF2)mRNA的m6A甲基化修饰。此外,NSC-Exos减少了小胶质细胞炎症反应对神经元的损伤。最后,小胶质细胞中NRF2过表达减弱了由NSE Exos中FTO敲低引起的小胶质细胞极化和神经元损伤的变化。这些发现表明,NSC-Exos通过转移FTO促进小胶质细胞的NRF2表达和M2极化,从而产生神经保护作用。
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Neural stem cell-derived exosomal FTO protects neuron from microglial inflammatory injury by inhibiting microglia NRF2 mRNA m6A modification.

Ischemic stroke (IS) can cause neuronal cell loss and function defects. Exosomes derived from neural stem cells (NSC-Exos) improve neural plasticity and promote neural function repair following IS. However, the potential mechanism remains unclear. In this study, NSC-Exos were characterized and co-cultured with microglia. We found that NSC-Exos increased NRF2 expression in oxygen-glucose deprivation/reoxygenation and LPS-induced microglia and converted microglia from M1 pro-inflammatory phenotype to M2 anti-inflammatory phenotype. NSC-Exos reduced m6A methylation modification of nuclear factor erythroid 2-related factor 2 (NRF2) mRNA via obesity-associated gene (FTO). Furthermore, NSC-Exos reduced the damage to neurons caused by microglia's inflammatory response. Finally, the changes in microglia polarization and neuron damage caused by FTO knockdown in NSE-Exos were attenuated by NRF2 overexpression in microglia. These findings revealed that NSC-Exos promotes NRF2 expression and M2 polarization of microglial via transferring FTO, thereby resulting in neuroprotective effects.

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来源期刊
Journal of neurogenetics
Journal of neurogenetics 医学-神经科学
CiteScore
4.40
自引率
0.00%
发文量
13
审稿时长
>12 weeks
期刊介绍: The Journal is appropriate for papers on behavioral, biochemical, or cellular aspects of neural function, plasticity, aging or disease. In addition to analyses in the traditional genetic-model organisms, C. elegans, Drosophila, mouse and the zebrafish, the Journal encourages submission of neurogenetic investigations performed in organisms not easily amenable to experimental genetics. Such investigations might, for instance, describe behavioral differences deriving from genetic variation within a species, or report human disease studies that provide exceptional insights into biological mechanisms
期刊最新文献
The initial years of the Cold Spring Harbor Laboratory summer course on the neurobiology of Drosophila. Clinical potential of epigenetic and microRNA biomarkers in PTSD. Molecular analysis of SMN2, NAIP, and GTF2H2 gene deletions and relationships with clinical subtypes of spinal muscular atrophy. Neurobiology of egg-laying behavior in Drosophila: neural control of the female reproductive system. Memoir of the early years of the CSHL summer Drosophila neurobiology course: 1984-1985.
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