microRNA-125b-5p alleviated CCI-induced neuropathic pain and modulated neuroinflammation via targeting SOX11.

IF 1.6 4区医学 Q4 NEUROSCIENCES Synapse Pub Date : 2024-09-01 DOI:10.1002/syn.22306

Liping Wang, Bei Wang, Xia Geng, Xiaona Guo, Tingting Wang, Jingjing Xu, Linkai Jiang, Haining Zhen

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Abstract

Background: Increasing evidence demonstrated the involvement of microRNAs (miRNAs) in the onset and development of neuropathic pain (NP). Exploring the molecular mechanism underlying NP and identifying key molecules could provide potential targets for the therapy of NP. The function and mechanism of miR-125b-5p in regulating NP have been studied, aiming to find a potential therapeutic target for NP.

Methods: NP rat models were established by the chronic constriction injury (CCI) method. The paw withdrawal threshold and paw withdrawal latency were assessed to evaluate the establishment and recovery of rats. Highly aggressive proliferating immortalized (HAPI) micoglia cell, a rat microglia cell line, was treated with lipopolysaccharide (LPS). The M1/M2 polarization and inflammation were evaluated by enzyme-linked immunosorbent assay and western blotting.

Results: Decreasing miR-125b-5p and increasing SOX11 were observed in CCI rats and LPS-induced HAPI cells. Overexpressing miR-125b-5p alleviated mechanical allodynia and thermal hyperalgesia and suppressed inflammation in CCI rats. LPS induced M1 polarization and inflammation of HAPI cells, which was attenuated by miR-125b-5p overexpression. miR-125-5p negatively regulated the expression of SOX11 in CCI rats and LPS-induced HAPI cells. Overexpressing SOX11 reversed the protective effects of miR-125b-5p on mechanical pain in CCI rats and the polarization and inflammation in HAPI cells, which was considered the mechanism underlying miR-125b-5p.

Conclusion: miR-125b-5p showed a protective effect on NP by regulating inflammation and polarization of microglia via negatively modulating SOX11.

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microRNA-125b-5p通过靶向SOX11缓解CCI诱导的神经病理性疼痛并调节神经炎症。

背景：越来越多的证据表明，微RNA（miRNA）参与了神经病理性疼痛（NP）的发生和发展。探索神经病理性疼痛的分子机制并确定关键分子可为治疗神经病理性疼痛提供潜在靶点。本研究对miR-125b-5p调控NP的功能和机制进行了研究，旨在寻找NP的潜在治疗靶点：方法：采用慢性收缩损伤（CCI）法建立 NP 大鼠模型。方法：采用慢性收缩性损伤（CCI）方法建立 NP 大鼠模型，评估大鼠爪退缩阈值和爪退缩潜伏期，以评价大鼠的建立和恢复情况。用脂多糖（LPS）处理大鼠小胶质细胞系--高侵袭性增殖永生（HAPI）小胶质细胞。通过酶联免疫吸附试验和免疫印迹法对 M1/M2 极化和炎症进行了评估：结果：在CCI大鼠和LPS诱导的HAPI细胞中观察到miR-125b-5p减少和SOX11增加。过表达 miR-125b-5p 可减轻 CCI 大鼠的机械异感和热痛，并抑制炎症。miR-125b-5p能负向调节SOX11在CCI大鼠和LPS诱导的HAPI细胞中的表达。结论：miR-125b-5p 通过负向调节 SOX11 来调节炎症和小胶质细胞的极化，从而对 NP 起保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Synapse 医学-神经科学

CiteScore

3.80

自引率

0.00%

发文量

审稿时长

4-8 weeks

期刊介绍： SYNAPSE publishes articles concerned with all aspects of synaptic structure and function. This includes neurotransmitters, neuropeptides, neuromodulators, receptors, gap junctions, metabolism, plasticity, circuitry, mathematical modeling, ion channels, patch recording, single unit recording, development, behavior, pathology, toxicology, etc.