转录因子 ETS 原癌基因 1 通过调节初级传入神经元中的组蛋白去乙酰化酶 1 促成神经性疼痛。

IF 2.8 3区 医学 Q2 NEUROSCIENCES
Hong-Li Zheng, Shi-Yu Sun, Tong Jin, Ming Zhang, Ying Zeng, Qiaoqiao Liu, Kehui Yang, Runa Wei, Zhiqiang Pan, Fuqing Lin
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引用次数: 0

摘要

神经损伤可诱导背根神经节(DRGs)中的离子通道、酶和细胞因子/趋化因子发生异常变化;这些变化是由转录因子引起的,或者至少部分是由转录因子控制的,而转录因子有助于神经性疼痛的发生。然而,人们对转录因子参与神经病理性疼痛的情况知之甚少。在这项研究中,我们报告了转录因子(TF)ETS原癌基因1(ETS1)是神经病理性疼痛的起始和发展所必需的。坐骨神经慢性收缩性损伤(CCI,一种临床神经病理性疼痛模型)会增加ETS1在受伤雄性小鼠DRG中的表达。阻断这种上调可减轻CCI引起的机械异感和热痛,但对运动功能无明显影响。从机理上讲,神经损伤诱导的 ETS1 上调会通过增强组蛋白去乙酰化酶 1(HDAC1,疼痛的关键启动因子)与 HDAC1 启动子的结合活性来促进其表达,从而导致脊髓中枢敏化的升高,脊髓背角 p-ERK1/2 和 GFAP 的表达增加就是证明。由此看来,DRG 中的 ETS1/HDAC1 轴可能在神经病理性疼痛的发生和维持中起着关键作用,而 ETS1 是神经病理性疼痛的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Transcription factor ETS proto-oncogene 1 contributes to neuropathic pain by regulating histone deacetylase 1 in primary afferent neurons.

Transcription factor ETS proto-oncogene 1 contributes to neuropathic pain by regulating histone deacetylase 1 in primary afferent neurons.

Transcription factor ETS proto-oncogene 1 contributes to neuropathic pain by regulating histone deacetylase 1 in primary afferent neurons.

Transcription factor ETS proto-oncogene 1 contributes to neuropathic pain by regulating histone deacetylase 1 in primary afferent neurons.

Nerve injury can induce aberrant changes in ion channels, enzymes, and cytokines/chemokines in the dorsal root ganglia (DRGs); these changes are due to or at least partly governed by transcription factors that contribute to the genesis of neuropathic pain. However, the involvement of transcription factors in neuropathic pain is poorly understood. In this study, we report that transcription factor (TF) ETS proto-oncogene 1 (ETS1) is required for the initiation and development of neuropathic pain. Sciatic nerve chronic constrictive injury (CCI, a clinical neuropathic pain model) increases ETS1 expression in the injured male mouse DRG. Blocking this upregulation alleviated CCI-induced mechanical allodynia and thermal hyperalgesia, with no apparent effect on locomotor function. Mimicking this upregulation results in the genesis of nociception hypersensitivity; mechanistically, nerve injury-induced ETS1 upregulation promotes the expression of histone deacetylase 1 (HDAC1, a key initiator of pain) via enhancing its binding activity to the HDAC1 promotor, leading to the elevation of spinal central sensitization, as evidenced by increased expression of p-ERK1/2 and GFAP in the dorsal spinal horn. It appears that the ETS1/HDAC1 axis in DRG may have a critical role in the development and maintenance of neuropathic pain, and ETS1 is a potential therapeutic target in neuropathic pain.

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来源期刊
Molecular Pain
Molecular Pain 医学-神经科学
CiteScore
5.60
自引率
3.00%
发文量
56
审稿时长
6-12 weeks
期刊介绍: Molecular Pain is a peer-reviewed, open access journal that considers manuscripts in pain research at the cellular, subcellular and molecular levels. Molecular Pain provides a forum for molecular pain scientists to communicate their research findings in a targeted manner to others in this important and growing field.
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