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成年斑马鱼脊髓损伤后的 microRNAs 调控。

Regulation of MicroRNAs After Spinal Cord Injury in Adult Zebrafish.

机构信息

Department of Orthopedics, the Second Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, 247 Beiyuan Street, Jinan, Shandong, 250033, China.

International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.

出版信息

J Mol Neurosci. 2024 Jul 11;74(3):66. doi: 10.1007/s12031-024-02242-2.

DOI:10.1007/s12031-024-02242-2
PMID:38990400
Abstract

Spinal cord injury (SCI) is a central nerve injury that often leads to loss of motor and sensory functions at or below the level of the injury. Zebrafish have a strong ability to repair after SCI, but the role of microRNAs (miRNAs) after SCI remains unclear. Locomotor behavior analysis showed that adult zebrafish recovered about 30% of their motor ability at 2 weeks and 55% at 3 weeks after SCI, reflecting their strong ability to repair SCI. Through miRNA sequencing, mRNA sequencing, RT-qPCR experiment verification, and bioinformatics predictive analysis, the key miRNAs and related genes in the repair of SCI were screened. A total of 38 miRNAs were significantly different, the top ten miRNAs were verified by RT-qPCR. The prediction target genes were verified by the mRNAs sequencing results at the same time point. Finally, 182 target genes were identified as likely to be networked regulated by the 38 different miRNAs. GO and KEGG enrichment analysis found that miRNAs targeted gene regulation of many key pathways, such as membrane tissue transport, ribosome function, lipid binding, and peroxidase activity. The PPI network analysis showed that miRNAs were involved in SCI repair through complex network regulation, among which dre-miR-21 may enhance cell reversibility through nop56, and that dre-miR-125c regulates axon growth through kpnb1 to repair SCI.

摘要

脊髓损伤 (SCI) 是一种中枢神经系统损伤,常导致损伤水平或以下的运动和感觉功能丧失。斑马鱼具有很强的 SCI 后修复能力,但 SCI 后 microRNAs (miRNAs) 的作用尚不清楚。运动行为分析表明,成年斑马鱼在 SCI 后 2 周和 3 周分别恢复了约 30%和 55%的运动能力,反映出其强大的 SCI 修复能力。通过 miRNA 测序、mRNA 测序、RT-qPCR 实验验证和生物信息学预测分析,筛选出 SCI 修复中的关键 miRNAs 和相关基因。共筛选到 38 个差异显著的 miRNAs,其中前 10 个 miRNAs 通过 RT-qPCR 进行验证。同时,根据同一时间点的 mRNAs 测序结果验证预测靶基因。最后,鉴定出 182 个靶基因,这些靶基因可能由 38 个不同的 miRNAs 进行网络调控。GO 和 KEGG 富集分析发现,miRNAs 靶向调控了许多关键通路的基因,如膜组织转运、核糖体功能、脂质结合和过氧化物酶活性。PPI 网络分析表明,miRNAs 通过复杂的网络调控参与 SCI 修复,其中 dre-miR-21 可能通过 nop56 增强细胞可逆性,dre-miR-125c 通过 kpnb1 调节轴突生长来修复 SCI。

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本文引用的文献

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The Promising Role of a Zebrafish Model Employed in Neural Regeneration Following a Spinal Cord Injury.斑马鱼模型在脊髓损伤后神经再生中的应用前景。
Int J Mol Sci. 2023 Sep 11;24(18):13938. doi: 10.3390/ijms241813938.
2
KPNB1-mediated nuclear import in cancer.KPNB1 介导的癌症核输入。
Eur J Pharmacol. 2023 Sep 15;955:175925. doi: 10.1016/j.ejphar.2023.175925. Epub 2023 Jul 18.
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Melatonin restores endoplasmic reticulum homeostasis to protect injured neurons in a rat model of chronic cervical cord compression.
褪黑素可恢复内质网稳态,以保护慢性颈髓压迫大鼠模型中受损的神经元。
J Pineal Res. 2023 May;74(4):e12859. doi: 10.1111/jpi.12859. Epub 2023 Mar 6.
4
A Zebrafish Loss-of-Function Model Exhibits a Severe Neurodegenerative Phenotype.一个斑马鱼功能丧失模型表现出严重的神经退行性表型。
Biomedicines. 2022 Jul 28;10(8):1814. doi: 10.3390/biomedicines10081814.
5
Effects of Methylprednisolone in the Treatment of Spinal Cord Injuries by Evaluation of microRNA-21: An Experimental Study.通过评估微小RNA-21研究甲基强的松龙治疗脊髓损伤的效果:一项实验研究
J Neurol Surg A Cent Eur Neurosurg. 2023 May;84(3):240-246. doi: 10.1055/s-0042-1743552. Epub 2022 Apr 19.
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Progression in translational research on spinal cord injury based on microenvironment imbalance.基于微环境失衡的脊髓损伤转化研究进展
Bone Res. 2022 Apr 8;10(1):35. doi: 10.1038/s41413-022-00199-9.
7
Inhibition of CDK1 attenuates neuronal apoptosis and autophagy and confers neuroprotection after chronic spinal cord injury in vivo.抑制 CDK1 可减轻慢性脊髓损伤后的神经元凋亡和自噬,并发挥神经保护作用。
J Chem Neuroanat. 2022 Jan;119:102053. doi: 10.1016/j.jchemneu.2021.102053. Epub 2021 Nov 25.
8
Identification of key genes involved in recovery from spinal cord injury in adult zebrafish.成年斑马鱼脊髓损伤恢复过程中关键基因的鉴定
Neural Regen Res. 2022 Jun;17(6):1334-1342. doi: 10.4103/1673-5374.327360.
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Blocking the EGFR/p38/NF-κB signaling pathway alleviates disruption of BSCB and subsequent inflammation after spinal cord injury.阻断 EGFR/p38/NF-κB 信号通路减轻脊髓损伤后血脑屏障破坏和随后的炎症反应。
Neurochem Int. 2021 Nov;150:105190. doi: 10.1016/j.neuint.2021.105190. Epub 2021 Sep 17.
10
miRNA-221 Regulates Spinal Cord Injury-Induced Inflammatory Response through Targeting TNF- Expression.miRNA-221 通过靶向 TNF-α 表达调控脊髓损伤诱导的炎症反应。
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