MiR-124 通过抑制 TRAF6 减少创伤性脑损伤后的神经炎症

IF 2.2 4区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Neuroimmunomodulation Pub Date : 2023-01-01 Epub Date: 2023-03-01 DOI:10.1159/000528502
Yongxiang Yang, Yuqin Ye, Kexia Fan, Jianing Luo, Yongjian Yang, Yuan Ma
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引用次数: 0

摘要

导言神经炎症会导致创伤性脑损伤(TBI)后的继发性损伤,而这种损伤主要是由小胶质细胞介导的。据报道,miR-124 通过靶向 TLR4 信号通路在小胶质细胞的极化中发挥重要作用。然而,miR-124 在 TBI 后由小胶质细胞介导的神经炎症中的作用和机制尚不清楚。为了澄清这一点,我们进行了这项研究:方法:首先通过 RT-PCR 检测创伤后 1/3/7 天受伤大脑中 miR-124 的表达。然后,在创伤后 24 小时内使用 miR-124 模拟物或抑制剂干扰 miR-124 的表达。随后,用 RT-PCR 检测小胶质细胞极化标记物,用 ELISA 检测炎症细胞因子的表达,用 WB 检测 TLR4/MyD88/IRAK1/TRAF6/NF-κB 的表达,用 NSS 和 MWM 测试评估神经功能缺损。最后,通过体外实验探索了 miR-124 在 TLR4 信号通路上的确切靶分子:结果:动物实验表明,创伤性脑损伤后,miR-124 的表达下调。miR-124的上调促进了小胶质细胞的M2极化,抑制了TLR4通路的活性,减轻了创伤性脑损伤后的神经炎症和神经功能缺损。体外实验表明,miR-124 通过抑制 TRAF6 促进了小胶质细胞的 M2 极化并减轻了神经炎症:这项研究表明,上调 miR-124 能促进小胶质细胞的 M2 极化,并通过抑制 TRAF6 减少创伤性脑损伤后的神经炎症。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
MiR-124 Reduced Neuroinflammation after Traumatic Brain Injury by Inhibiting TRAF6.

Introduction: Neuroinflammation contributes to secondary injury after traumatic brain injury (TBI), which has been mainly mediated by the microglia. MiR-124 was reported to play an important role in the polarization of microglia by targeting TLR4 signaling pathway. However, the role and mechanism of miR-124 in neuroinflammation mediated by microglia after TBI is unclear. To clarify this, we performed this research.

Methods: The expression of miR-124 was first measured by RT-PCR in the injured brain at 1/3/7 days post-TBI. Then, miR-124 mimics or inhibitors administration was used to interfere the expression of miR-124 at 24 h post-TBI. Subsequently, the microglia polarization markers were detected by RT-PCR, the expression of inflammatory cytokines was detected by ELISA, the expression of TLR4/MyD88/IRAK1/TRAF6/NF-κB was measured by WB, and the neurological deficit was evaluated by NSS and MWM test. At last, in vitro experiments were performed to explore the exact target molecule of miR-124 on TLR4 signaling pathway.

Results: Animal research indicated that the expression of miR-124 was downregulated after TBI. Upregulation of miR-124 promoted the M2 polarization of microglia and inhibited the activity of TLR4 pathway, as well as reduced neuroinflammation and neurological deficit after TBI. In vitro experiments indicated that miR-124 promoted the M2 polarization of microglia and reduced neuroinflammation by inhibiting TRAF6.

Conclusion: This study demonstrated that upregulation of miR-124 promoted the M2 polarization of microglia and reduced neuroinflammation after TBI by inhibiting TRAF6.

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来源期刊
Neuroimmunomodulation
Neuroimmunomodulation 医学-免疫学
CiteScore
3.60
自引率
4.20%
发文量
35
审稿时长
>12 weeks
期刊介绍: The rapidly expanding area of research known as neuroimmunomodulation explores the way in which the nervous system interacts with the immune system via neural, hormonal, and paracrine actions. Encompassing both basic and clinical research, ''Neuroimmunomodulation'' reports on all aspects of these interactions. Basic investigations consider all neural and humoral networks from molecular genetics through cell regulation to integrative systems of the body. The journal also aims to clarify the basic mechanisms involved in the pathogenesis of the CNS pathology in AIDS patients and in various neurodegenerative diseases. Although primarily devoted to research articles, timely reviews are published on a regular basis.
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