MiRNA-107 contributes to inflammatory pain by down-regulating GLT-1 expression in rat spinal dorsal horn
MiRNA-107 contributes to inflammatory pain by down-regulating GLT-1 expression in rat spinal dorsal horn
复制标题
miRNA-107 通过下调大鼠脊髓背角 GLT-1 表达导致炎症性疼痛
DOI：
10.1002/ejp.1745
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发表时间：
2021
影响因子：
3.6
通讯作者：
Zhang Ping-An
中科院分区：
文献类型：
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作者：
Zhang Ling;Wu Rui;Xu Mei-Jie;Sha Jie;Xu Guang-Yin;Wu Jian;Zhang Ping-An
背景：炎症性疼痛是影响患者生活质量的严重临床问题。然而，目前可用的治疗炎症性疼痛的方法效果有限，甚至会引起严重的副作用。本研究的目的是探讨miRNA‐107和谷氨酸转运蛋白1 （GLT‐1）在完全弗氏佐剂（CFA）诱导的大鼠炎症性疼痛中的作用。方法采用von Frey纤维丝法测定大鼠的拔肌阈值（PWT）。采用实时定量PCR和western blotting检测大鼠腰椎背角（L4 ~ L6）组织中miRNA‐107和GLT‐1的表达。采用荧光原位杂交和荧光免疫组化检测miRNA‐107、GLT‐1的表达以及miRNA‐107与GLT‐1的共定位。结果注射CFA可显著降低大鼠PWT。CFA大鼠脊髓背角miRNA‐107表达水平明显上调，GLT‐1表达水平明显降低。miRNA‐107和GLT‐1在CFA大鼠脊髓背角的相同细胞中共表达。头孢曲松是GLT‐1的选择性激活剂，可明显增加CFA大鼠的PWT。此外，miRNA‐107的安他哥莫逆转GLT‐1的下调，减轻CFA诱导的CFA大鼠机械异常性疼痛。这些结果表明miR - 107的增加通过下调GLT - 1的表达来促进炎症性疼痛，这意味着一种有希望的疼痛治疗策略。意义目前治疗炎症性疼痛的方法效果有限，甚至有严重的副作用。mirna可能在炎症性疼痛中具有重要的诊断和治疗潜力。在本研究中，我们揭示了CFA诱导的大鼠炎性疼痛模型中异常性疼痛的潜在脊柱机制。miR - 107的增加通过靶向和下调GLT - 1的表达而促进炎症性疼痛，这意味着一种有希望的炎症性疼痛治疗策略。
BackgroundInflammatory pain is a severe clinical problem that affects the quality of life in patients. However, the currently available treatments for inflammatory pain have limited effect and even causes severe side effects. The aim of this study was to investigate the roles of miRNA‐107 and glutamate transporter 1 (GLT‐1) in the inflammatory pain of rats induced by complete Freund's adjuvant (CFA).MethodsPaw withdrawal threshold (PWT) of rats was measured by von Frey Filaments. The expressions of miRNA‐107 and GLT‐1 in the lumbar spinal dorsal horn (L4‐L6) were measured with real‐time quantitative PCR and western blotting analysis. Fluorescent in situ hybridization and fluorescent‐immunohistochemistry were employed to detect the expression of miRNA‐107, GLT‐1 and co‐location of miRNA‐107 with GLT‐1.ResultsInjection of CFA significantly reduced PWT of rats. The miRNA‐107 expression level was obviously up‐regulated while the GLT‐1 expression level was decreased in the spinal dorsal horn of CFA rats. miRNA‐107 and GLT‐1 were co‐expressed in the same cells of the spinal dorsal horn in CFA rats. Ceftriaxone, a selective activator of GLT‐1, obviously increased the PWT of CFA rats. Furthermore, antagomir of miRNA‐107 reversed the down‐regulation of GLT‐1 and alleviated CFA‐induced mechanical allodynia of CFA rats.ConclusionsThese results suggest that an increase of miR‐107 contributes to inflammatory pain through downregulating GLT‐1 expression, implying a promising strategy for pain therapy.SignificanceThe currently available treatments for inflammatory pain has limited effect even causes severe side effects. MiRNAs may have important diagnostic and therapeutic potential in inflammatory pain. In present study, we show a potential spinal mechanism of allodynia in rat inflammatory pain model induced by CFA. Increased miR‐107 contribute to inflammatory pain by targeting and downregulating GLT‐1 expression, implying a promising strategy for inflammatory pain.