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周围神经损伤后雪旺细胞中CD146的上调调节再生过程中的雪旺细胞功能。

Up-Regulation of CD146 in Schwann Cells Following Peripheral Nerve Injury Modulates Schwann Cell Function in Regeneration.

作者信息

Shen Yinying, Zhu Jun, Liu Qianyan, Ding Shiyan, Dun Xinpeng, He Jianghong

机构信息

Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Tissue Engineering Technology Products, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.

Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China.

出版信息

Front Cell Neurosci. 2021 Oct 14;15:743532. doi: 10.3389/fncel.2021.743532. eCollection 2021.

DOI:10.3389/fncel.2021.743532
PMID:34720881
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8552958/
Abstract

CD146 is cell adhesion molecule and is implicated in a variety of physiological and pathological processes. However, the involvement of CD146 in peripheral nerve regeneration has not been studied yet. Here, we examine the spatial and temporal expression pattern of CD146 in injured mouse sciatic nerve via high-throughput data analysis, RT-PCR and immunostaining. By microarray data analysis and RT-PCR validation, we show that CD146 mRNA is significantly up-regulated in the nerve bridge and in the distal nerve stump following mouse sciatic nerve transection injury. By single cell sequencing data analysis and immunostaining, we demonstrate that CD146 is up-regulated in Schwann cells and cells associated with blood vessels following mouse peripheral nerve injury. Bioinformatic analysis revealed that CD146 not only has a key role in promoting of blood vessel regeneration but also regulates cell migration. The biological function of CD146 in Schwann cells was further investigated by knockdown of CD146 in rat primary Schwann cells. Functional assessments showed that knockdown of CD146 decreases viability and proliferation of Schwann cells but increases Schwann cell migration. Collectively, our findings imply that CD146 could be a key cell adhesion molecule that is up-regulated in injured peripheral nerves to regulate peripheral nerve regeneration.

摘要

CD146是一种细胞粘附分子,参与多种生理和病理过程。然而,CD146在周围神经再生中的作用尚未得到研究。在此,我们通过高通量数据分析、逆转录-聚合酶链反应(RT-PCR)和免疫染色,研究了CD146在小鼠坐骨神经损伤后的时空表达模式。通过微阵列数据分析和RT-PCR验证,我们发现小鼠坐骨神经横断损伤后,神经桥和远端神经残端中的CD146 mRNA显著上调。通过单细胞测序数据分析和免疫染色,我们证明小鼠周围神经损伤后,雪旺细胞和血管相关细胞中的CD146上调。生物信息学分析表明,CD146不仅在促进血管再生中起关键作用,还调节细胞迁移。通过在大鼠原代雪旺细胞中敲低CD146,进一步研究了CD146在雪旺细胞中的生物学功能。功能评估表明,敲低CD146会降低雪旺细胞的活力和增殖,但会增加雪旺细胞的迁移。总的来说,我们的研究结果表明,CD146可能是一种关键的细胞粘附分子,在损伤的周围神经中上调,以调节周围神经再生。

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本文引用的文献

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RSC Adv. 2019 Apr 5;9(19):10760-10765. doi: 10.1039/c9ra01710k. eCollection 2019 Apr 3.
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Single Cell Transcriptome Data Analysis Defines the Heterogeneity of Peripheral Nerve Cells in Homeostasis and Regeneration.单细胞转录组数据分析揭示了稳态和再生过程中外周神经细胞的异质性。
Front Cell Neurosci. 2021 Mar 22;15:624826. doi: 10.3389/fncel.2021.624826. eCollection 2021.
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Betacellulin regulates peripheral nerve regeneration by affecting Schwann cell migration and axon elongation.
Neural Regen Res. 2024 Feb;19(2):380-386. doi: 10.4103/1673-5374.377588.
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β细胞素通过影响施万细胞迁移和轴突伸长来调节周围神经再生。
Mol Med. 2021 Mar 25;27(1):27. doi: 10.1186/s10020-021-00292-5.
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MCAM/CD146 Signaling PLCγ1 Leads to Activation of β-Integrins in Memory T-Cells Resulting in Increased Brain Infiltration.MCAM/CD146 信号 PLCγ1 导致记忆 T 细胞中 β-整合素的激活,从而导致大脑浸润增加。
Front Immunol. 2020 Dec 14;11:599936. doi: 10.3389/fimmu.2020.599936. eCollection 2020.
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FGF5 Regulates Schwann Cell Migration and Adhesion.成纤维细胞生长因子5调节雪旺细胞的迁移和黏附。
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Glia. 2021 Feb;69(2):235-254. doi: 10.1002/glia.23892. Epub 2020 Jul 22.
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