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E2F4促进斑马鱼脊髓损伤后的神经元再生和功能恢复。

E2F4 Promotes Neuronal Regeneration and Functional Recovery after Spinal Cord Injury in Zebrafish.

作者信息

Sasagawa Shota, Nishimura Yuhei, Hayakawa Yuka, Murakami Soichiro, Ashikawa Yoshifumi, Yuge Mizuki, Okabe Shiko, Kawaguchi Koki, Kawase Reiko, Tanaka Toshio

机构信息

Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine Tsu, Japan.

Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of MedicineTsu, Japan; Mie University Medical Zebrafish Research CenterTsu, Japan; Department of Systems Pharmacology, Mie University Graduate School of MedicineTsu, Japan; Department of Omics Medicine, Mie University Industrial Technology Innovation InstituteTsu, Japan; Department of Bioinformatics, Mie University Life Science Research CenterTsu, Japan.

出版信息

Front Pharmacol. 2016 May 9;7:119. doi: 10.3389/fphar.2016.00119. eCollection 2016.

DOI:10.3389/fphar.2016.00119
PMID:27242526
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4860404/
Abstract

Mammals exhibit poor recovery after spinal cord injury (SCI), whereas non-mammalian vertebrates exhibit significant spontaneous recovery after SCI. The mechanisms underlying this difference have not been fully elucidated; therefore, the purpose of this study was to investigate these mechanisms. Using comparative transcriptome analysis, we demonstrated that genes related to cell cycle were significantly enriched in the genes specifically dysregulated in zebrafish SCI. Most of the cell cycle-related genes dysregulated in zebrafish SCI were down-regulated, possibly through activation of e2f4. Using a larval zebrafish model of SCI, we demonstrated that the recovery of locomotive function and neuronal regeneration after SCI were significantly inhibited in zebrafish treated with an E2F4 inhibitor. These results suggest that activation of e2f4 after SCI may be responsible, at least in part, for the significant recovery in zebrafish. This provides novel insight into the lack of recovery after SCI in mammals and informs potential therapeutic strategies.

摘要

哺乳动物脊髓损伤（SCI）后恢复能力较差，而非哺乳动物脊椎动物SCI后则表现出显著的自发恢复。这种差异背后的机制尚未完全阐明；因此，本研究的目的是探究这些机制。通过比较转录组分析，我们证明与细胞周期相关的基因在斑马鱼SCI中特异性失调的基因中显著富集。斑马鱼SCI中失调的大多数细胞周期相关基因被下调，可能是通过e2f4的激活。使用斑马鱼幼虫SCI模型，我们证明在用E2F4抑制剂处理的斑马鱼中，SCI后运动功能的恢复和神经元再生受到显著抑制。这些结果表明，SCI后e2f4的激活可能至少部分地导致了斑马鱼的显著恢复。这为哺乳动物SCI后缺乏恢复提供了新的见解，并为潜在的治疗策略提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/4860404/de5e7c9d26fe/fphar-07-00119-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/4860404/00bdf84628bb/fphar-07-00119-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/4860404/ba783ff513f0/fphar-07-00119-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/4860404/12bbe0ed3d26/fphar-07-00119-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/4860404/de5e7c9d26fe/fphar-07-00119-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/4860404/00bdf84628bb/fphar-07-00119-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/4860404/ba783ff513f0/fphar-07-00119-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/4860404/12bbe0ed3d26/fphar-07-00119-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1182/4860404/de5e7c9d26fe/fphar-07-00119-g0005.jpg

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