Upstream stimulating factor 2 aggravates neuropathic pain induced in spinal nerve ligation-induced mice via regulating SNHG5/miR-181b-5p.

IF 2.3 4区医学 Q2 DEVELOPMENTAL BIOLOGY Developmental Neuroscience Pub Date : 2024-03-12 DOI:10.1159/000538178

Mi Chen, Yang Yang, Jiatian Cui, Li Qiu, Xiaohua Zou, Xianggang Zeng

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Abstract

Background: Upstream stimulating factor 2 (USF2) belongs to basic-Helix-Loop-Helix-Leucine Zipper transcription factor family, regulating expression of genes involved in immune response or energy metabolism network. Role of USF2 in neuropathic pain was evaluated.

Methods: Mice were intraspinally injected with adenovirus for knockdown of USF2 (Ad-shUSF2), and then subjected to spinal nerve ligation (SNL) to induce neuropathic pain. Distribution and expression of USF2 was detected by western blot and immunofluorescence. Mechanical and thermal pain sensitivity were examined by paw withdrawal thresholds (PWT) and paw withdrawal latency (PWL). Chromatin immunoprecipitation (ChIP) and luciferase activity assays were performed to detect binding ability between USF2 and SNHG5.

Results: The expression of USF2 was elevated and colocalized with astrocytes and microglia in L5 dorsal root ganglion (DRG) of SNL-induced mice. Injection of Ad-shUSF2 attenuated SNL-induced decrease of PWT and PWL in mice. Knockdown of USF2 increased level of IL-10, but decreased TNF-α, IL-1β, and IL-6 in SNL-induced mice. Silence of USF2 enhanced protein expression of CD206, while reduced expression of CD16 and CD32 in SNL-induced mice. USF2 bind to promoter of SNHG5, and weakened SNL-induced up-regulation of SNHG5. SNHG5 bind to miR-181b-5p, and miR-181b-5p to interact with CXCL5.

Conclusion: Silence of USF2 ameliorated neuropathic pain, suppressed activation of M1 microglia and inhibited inflammation in SNL-induced mice through regulation of SNHG5/miR-181b-5p/CXCL5 axis. Therefore, USF2/SNHG5/miR-181b-5p/CXCL5 might be a promising target for neuropathic pain. However, the effect of USF2/SNHG5/miR-181b-5p/CXCL5 on neuropathic pain should also be investigated in further research.

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上游刺激因子2通过调节SNHG5/miR-181b-5p加重脊神经结扎诱导小鼠的神经病理性疼痛

背景：上游刺激因子2（USF2）属于碱性-髓质-环状-髓质-亮氨酸拉链转录因子家族，调节参与免疫反应或能量代谢网络的基因表达。本研究评估了 USF2 在神经病理性疼痛中的作用：方法：给小鼠鞘内注射腺病毒以敲除 USF2（Ad-shUSF2），然后进行脊神经结扎（SNL）以诱导神经病理性疼痛。通过Western印迹和免疫荧光检测USF2的分布和表达。通过爪退缩阈值（PWT）和爪退缩潜伏期（PWL）检测机械痛和热痛的敏感性。进行了染色质免疫沉淀（ChIP）和荧光素酶活性测定，以检测USF2和SNHG5之间的结合能力：结果：在SNL诱导的小鼠L5背根神经节（DRG）中，USF2的表达升高，并与星形胶质细胞和小胶质细胞共定位。注射 Ad-shUSF2 可减轻 SNL 诱导的小鼠脉搏波速度和脉搏波速度的下降。在SNL诱导的小鼠中，敲除USF2会增加IL-10的水平，但会降低TNF-α、IL-1β和IL-6的水平。在SNL诱导的小鼠中，沉默USF2可提高CD206的蛋白表达，同时降低CD16和CD32的表达。USF2 与 SNHG5 启动子结合，削弱了 SNL 诱导的 SNHG5 上调。SNHG5与miR-181b-5p结合，miR-181b-5p与CXCL5相互作用：结论：通过调节 SNHG5/miR-181b-5p/CXCL5 轴，沉默 USF2 可改善 SNL 诱导小鼠的神经病理性疼痛、抑制 M1 小胶质细胞的活化并抑制炎症。因此，USF2/SNHG5/miR-181b-5p/CXCL5可能是治疗神经病理性疼痛的一个有前景的靶点。不过，USF2/SNHG5/miR-181b-5p/CXCL5 对神经病理性疼痛的影响还需要进一步研究。

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来源期刊

Developmental Neuroscience 医学-发育生物学

CiteScore

4.00

自引率

3.40%

发文量

审稿时长

>12 weeks

期刊介绍： ''Developmental Neuroscience'' is a multidisciplinary journal publishing papers covering all stages of invertebrate, vertebrate and human brain development. Emphasis is placed on publishing fundamental as well as translational studies that contribute to our understanding of mechanisms of normal development as well as genetic and environmental causes of abnormal brain development. The journal thus provides valuable information for both physicians and biologists. To meet the rapidly expanding information needs of its readers, the journal combines original papers that report on progress and advances in developmental neuroscience with concise mini-reviews that provide a timely overview of key topics, new insights and ongoing controversies. The editorial standards of ''Developmental Neuroscience'' are high. We are committed to publishing only high quality, complete papers that make significant contributions to the field.