Profile of the RNA in exosomes from astrocytes and microglia using deep sequencing: implications for neurodegeneration mechanisms.

Profile of the RNA in exosomes from astrocytes and microglia using deep sequencing: implications for neurodegeneration mechanisms.
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使用深度测序分析星形胶质细胞和小胶质细胞外泌体中的 RNA 概况:对神经退行性变机制的影响

DOI:
10.4103/1673-5374.320999
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发表时间:
2022-03
影响因子:
6.1
通讯作者:
Zhou SL
Zhou SL
中科院分区:
医学2区
文献类型:
--
作者:
Xie HM;Su X;Zhang FY;Dai CL;Wu RH;Li Y;Han XX;Feng XM;Yu B;Zhu SX;Zhou SL

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参考文献

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神经胶质细胞在中枢神经系统的信号转导、能量代谢、细胞外离子稳态和神经保护等方面发挥重要作用。然而,很少有研究解释来自神经胶质细胞的外泌体对中枢神经系统健康和疾病的潜在影响。在这项研究中,通过深度RNA测序鉴定了来自星形胶质细胞和小胶质细胞的外泌体中表达的基因。京都基因百科全书和基因组分析表明,这些外泌体中的几种途径导致神经退行性疾病,包括阿尔茨海默病、帕金森病和亨廷顿病。基因本体分析表明,细胞外外的外来体,candion和生长因子活性富集在外来体从独特的星形胶质细胞组,而细胞外的外来体和candion富集在外来体从独特的小胶质细胞组。接下来,结合hub基因的筛选,蛋白质-蛋白质相互作用网络分析表明,来自星形胶质细胞的exosome通过代谢平衡和泛素依赖的蛋白质平衡影响神经退行性疾病,而来自小胶质细胞的exosome通过免疫炎症和氧化应激影响神经退行性疾病。尽管来自星形胶质细胞和小胶质细胞的外泌体之间的RNA表达存在差异,但这些组与枢纽基因、泛素B和热休克蛋白家族A(Hsp 70)成员8相关。泛素B具有多种调节功能,包括免疫调节、炎症抑制、蛋白催化、细胞内蛋白转运、外泌体和氧化应激等。结果揭示了神经胶质细胞外泌体在神经退行性疾病中的临床意义。本研究于2018年1月2日获得南通大学动物伦理委员会批准(批准号:S20180102-152)。
Glial cells play an important role in signal transduction, energy metabolism, extracellular ion homeostasis and neuroprotection of the central nervous system. However, few studies have explained the potential effects of exosomes from glial cells on central nervous system health and disease. In this study, the genes expressed in exosomes from astrocytes and microglia were identified by deep RNA sequencing. Kyoto Encyclopedia of Genes and Genomes analysis indicated that several pathways in these exosomes are responsible for promoting neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Gene ontology analysis showed that extracellular exosome, mitochondrion and growth factor activity were enriched in exosomes from the unique astrocyte group, while extracellular exosome and mitochondrion were enriched in exosomes from the unique microglia group. Next, combined with the screening of hub genes, the protein-protein interaction network analysis showed that exosomes from astrocytes influence neurodegenerative diseases through metabolic balance and ubiquitin-dependent protein balance, whereas exosomes from microglia influence neurodegenerative diseases through immune inflammation and oxidative stress. Although there were differences in RNA expression between exosomes from astrocytes and microglia, the groups were related by the hub genes, ubiquitin B and heat shock protein family A (Hsp70) member 8. Ubiquitin B appeared to be involved in pleiotropic regulatory functions, including immune regulation, inflammation inhibition, protein catabolism, intracellular protein transport, exosomes and oxidative stress. The results revealed the clinical significance of exosomes from glia in neurodegenerative diseases. This study was approved by the Animal Ethics Committee of Nantong University, China (approval No. S20180102-152) on January 2, 2018.
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