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Fragile X mental retardation protein-regulated proinflammatory cytokine expression in the spinal cord contributes to the pathogenesis of inflammatory pain induced by complete Freund's adjuvant
Journal of Neurochemistry ( IF 4.2 ) Pub Date : 2021-08-02 , DOI: 10.1111/jnc.15485
Yixin Yang 1, 2 , Jinsong Zhao 1, 3 , Yunze Li 1 , Xiangyao Li 4 , Xiaowei Chen 5 , Zhiying Feng 1
Affiliation  

Studies have verified that Fragile X mental retardation protein (FMRP), an RNA-binding protein, plays a potential role in the pathogenesis of formalin- and (RS)-3,5-dihydroxyphenylglycine-induced abnormal pain sensations. However, the role of FMRP in inflammatory pain has not been reported. Here, we showed an increase in FMRP expression in the spinal dorsal horn (SDH) in a rat model of inflammatory pain induced by complete Freund's adjuvant (CFA). Double immunofluorescence staining revealed that FMRP was mainly expressed in spinal neurons and colocalized with proinflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)]. After consecutive intrathecal injection of fragile X mental retardation 1 small interfering RNA for 3 days post-CFA injection, FMRP expression in the SDH was reduced, and CFA-induced hyperalgesia was decreased. In addition, the CFA-induced increase in spinal TNF-α and IL-6 production was significantly suppressed by intrathecal administration of fragile X mental retardation 1 small interfering RNA. Together, these results suggest that FMRP regulates TNF-α and IL-6 levels in the SDH and plays an important role in inflammatory pain.

中文翻译:

脊髓中脆性 X 智力低下蛋白调节的促炎细胞因子表达有助于完全弗氏佐剂诱导的炎性疼痛的发病机制

研究已经证实脆性 X 智力低下蛋白 (FMRP),一种 RNA 结合蛋白,在福尔马林和 (RS)-3,5-二羟基苯基甘氨酸诱导的异常痛觉的发病机制中发挥潜在作用。然而,FMRP 在炎症性疼痛中的作用尚未见报道。在这里,我们在完全弗氏佐剂 (CFA) 诱导的炎症性疼痛大鼠模型中显示脊髓背角 (SDH) 中 FMRP 表达增加。双免疫荧光染色显示 FMRP 主要在脊髓神经元中表达,并与促炎细胞因子 [肿瘤坏死因子-α (TNF-α) 和白细胞介素-6 (IL-6)] 共定位。在 CFA 注射后连续鞘内注射脆性 X 智力低下 1 小干扰 RNA 3 天后,SDH 中的 FMRP 表达降低,CFA 引起的痛觉过敏减少。此外,CFA 诱导的脊髓 TNF-α 和 IL-6 产生的增加被脆弱 X 智力低下 1 小干扰 RNA 鞘内给药显着抑制。总之,这些结果表明 FMRP 调节 SDH 中的 TNF-α 和 IL-6 水平,并在炎症性疼痛中起重要作用。
更新日期:2021-08-02
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