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Toll样受体4(TLR4)通过ERK-NF-κB通路促进坐骨神经损伤后背根神经节的再生与修复。

Toll-Like Receptor 4 (TLR4) Promotes DRG Regeneration and Repair after Sciatic Nerve Injury via the ERK-NF-kB Pathway.

作者信息

Xia Yiming, Yao Yi, Feng Yumei, Zhou Yiyue, Jiang Maorong, Ding Zihan, Qian Jiaxi, Bai Huiyuan, Cai Min, Yao Dengbing

机构信息

Medical School of Nantong University, No. 19 Qixiu Road, Nantong, Jiangsu, 226001, People's Republic of China.

School of Public Health, Nantong University, Nantong, Jiangsu, 226019, People's Republic of China.

出版信息

Mol Neurobiol. 2025 Apr;62(4):4172-4189. doi: 10.1007/s12035-024-04483-z. Epub 2024 Oct 17.

DOI:10.1007/s12035-024-04483-z
PMID:39420131
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11880167/
Abstract

Previously, we found that the expression of Toll-like receptor 4 (TLR4) is altered after sciatic nerve injury, and its differential expression plays a key role in recovery. However, the mechanisms by which TLR4 affects neuronal function in the dorsal root ganglion (DRG) have not been completely evaluated. The objective is to determine TLR4 expression in DRG tissues after sciatic neural injury and exploring the effects of TLR4 knockdown and overexpression in the DRG on neuronal function and nerve regeneration in rats in vivo and in vitro. We established a model of nerve injury and utilized molecular biology and cell biology experiments to explore the molecular mechanisms by which TLR4 in the DRG affects sciatic nerve restoration and regeneration after injury. Verified the localization of TLR4 in DRG neurons. Investigated pathways that related to apoptosis or nerve regeneration by which TLR4 regulates the function of DRG neurons. TLR4 expression was upregulated in the DRG tissues of rats after sciatic nerve injury. TLR4 overexpression promoted axon regeneration and inhibited apoptosis in DRG neurons. TLR4 promoted the regeneration of axons and the recovery of motor and sensory functions in the sciatic nerve after injury in vivo, and the data showed that TLR4 may regulate the function of DRG neurons and promote nerve repair and regeneration through the ERK and NF-κB signaling pathways in vivo and ex vivo. The study suggests that TLR4 may regulate the function of DRG neurons and promote nerve regeneration by affecting the ERK and NF-κB signaling pathways.

摘要

此前,我们发现坐骨神经损伤后Toll样受体4(TLR4)的表达发生改变,其差异表达在恢复过程中起关键作用。然而,TLR4影响背根神经节(DRG)神经元功能的机制尚未得到全面评估。目的是确定坐骨神经损伤后DRG组织中TLR4的表达,并探讨在体内和体外敲低和过表达DRG中的TLR4对大鼠神经元功能和神经再生的影响。我们建立了神经损伤模型,并利用分子生物学和细胞生物学实验来探索DRG中的TLR4影响损伤后坐骨神经修复和再生的分子机制。验证了TLR4在DRG神经元中的定位。研究了TLR4调节DRG神经元功能的与细胞凋亡或神经再生相关的途径。坐骨神经损伤后大鼠DRG组织中TLR4表达上调。TLR4过表达促进DRG神经元轴突再生并抑制细胞凋亡。在体内,TLR4促进损伤后坐骨神经轴突再生以及运动和感觉功能的恢复,数据表明TLR4可能在体内和体外通过ERK和NF-κB信号通路调节DRG神经元的功能并促进神经修复和再生。该研究表明,TLR4可能通过影响ERK和NF-κB信号通路来调节DRG神经元的功能并促进神经再生。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/11880167/083819e9a013/12035_2024_4483_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/11880167/5a9b224bd4ee/12035_2024_4483_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/11880167/083819e9a013/12035_2024_4483_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/11880167/b10ae7b35f68/12035_2024_4483_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/11880167/8e544495f569/12035_2024_4483_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/11880167/10dd95e67b61/12035_2024_4483_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/11880167/1cf8a1d3a8e7/12035_2024_4483_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/11880167/de30751c4d36/12035_2024_4483_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/11880167/3fb9cf2dbdc9/12035_2024_4483_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/11880167/5a9b224bd4ee/12035_2024_4483_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8006/11880167/083819e9a013/12035_2024_4483_Fig8_HTML.jpg

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