SGK1-HDAC4-HMGB1 signaling pathway in the spinal cord dorsal horn participates in diabetic neuropathic pain.

IF 2.8 3区医学 Q2 NEUROSCIENCES Molecular Pain Pub Date : 2025-01-01 DOI:10.1177/17448069251321143

Mao-Biao Zhang, Jia-Li Chen, Jia-Hui Lu, Gai-Li Jia, Hong Cao, Jun Li

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Abstract

Purpose: This study aimed to determine whether serum-and glucocorticoid-inducible kinase1 (SGK1) activation-dependent histone deacetylase 4 (HDAC4) phosphorylation, nucleocytoplasmic trafficking, and subsequent regulation of high-mobility group protein box 1 (HMGB1) expression are involved in type 2 diabetic neuropathic pain (DNP).

Methods: The type 2 diabetic neuropathic pain model was established in rats by feeding them with a high-fat and high-sugar diet for 8 weeks and then fasting them for 12 h, followed by a single intraperitoneal injection of streptozotocin (STZ, 35 mg/kg). SGK1 was inhibited in the spinal cord by intrathecal administration of the SGK1 inhibitor GSK-650394.

Results: The present study revealed that pSGK1/tSGK1 was persistently upregulated in the spinal cord of rats with type-2 DNP. The downregulation of pSGK1/tSGK1 through the intrathecal injection of the SGK1 inhibitor GSK-650394 significantly ameliorated the pain hypersensitivity, relieved the abnormal expression of pHDAC4/tHDAC4 and HMGB1, and affected HDAC4 nucleocytoplasmic trafficking in DNP rats.

Conclusion: Our data suggest that SGK1 in the spinal cord modulates type-2 DNP by regulating the HDAC4/HMGB1 pathway.

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EXPRESS：脊髓背角SGK1-HDAC4-HMGB1信号通路参与糖尿病神经性疼痛。

目的：本研究旨在确定血清和糖皮质激素诱导的激酶1 （SGK1）激活依赖的组蛋白去乙酰化酶4 （HDAC4）磷酸化、核细胞质转运以及随后的高迁移率组蛋白盒1 （HMGB1）表达调控是否与2型糖尿病神经性疼痛（DNP）有关。方法：采用高脂高糖喂养大鼠8周后禁食12 h，腹腔注射链脲佐菌素（STZ, 35mg/kg）建立2型糖尿病神经性疼痛模型。脊髓鞘内给药SGK1抑制剂GSK-650394可抑制SGK1。结果：本研究发现，2型DNP大鼠脊髓中pSGK1/tSGK1持续上调。通过鞘内注射SGK1抑制剂GSK-650394下调pSGK1/tSGK1可显著改善DNP大鼠的疼痛超敏反应，缓解pHDAC4/tHDAC4和HMGB1的异常表达，影响HDAC4核质转运。结论：我们的数据表明脊髓中的SGK1通过调节HDAC4/HMGB1通路调节2型DNP。

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

Molecular Pain 医学-神经科学

CiteScore

5.60

自引率

3.00%

发文量

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.