JMJD8 通过影响脊髓星形胶质细胞分化来调节神经病理性疼痛。
JMJD8 regulates neuropathic pain by affecting spinal cord astrocyte differentiation.
机构信息
Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200437, China.
State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China.
出版信息
Neurosci Lett. 2023 Jul 13;809:137307. doi: 10.1016/j.neulet.2023.137307. Epub 2023 May 19.
The demethylase JmjC structural domain-containing protein 8 (JMJD8) has been demonstrated to be involved in cellular inflammatory responses. Neuropathic pain (NP) is a chronic pain, and it is unclear whether JMJD8 is involved in the regulation of NP. Using a chronic constriction injury (CCI) mouse model of NP, we investigated the expression levels of JMJD8 during NP and the influences of JMJD8 on regulating pain sensitivity. We found that JMJD8 expression in the spinal dorsal horn was reduced after CCI. Immunohistochemistry showed that JMJD8 was colabeled with GFAP in naïve mice. Knockdown of JMJD8 in the spinal dorsal horn astrocytes induced pain behavior. Further study showed that overexpression of JMJD8 in the spinal dorsal horn astrocytes not only reversed pain behavior but also activated the spinal dorsal horn A1 astrocytes. These results suggest that JMJD8 may modulate pain sensitivity by affecting activated the spinal dorsal horn A1 astrocytes and may be a potential therapeutic target for NP.
去甲基酶 JmjC 结构域包含蛋白 8（JMJD8）已被证明参与细胞炎症反应。神经病理性疼痛（NP）是一种慢性疼痛，目前尚不清楚 JMJD8 是否参与 NP 的调节。本研究使用慢性压迫损伤（CCI）NP 小鼠模型，研究了 JMJD8 在 NP 期间的表达水平，以及 JMJD8 对调节痛觉敏感性的影响。结果发现，CCI 后脊髓背角的 JMJD8 表达减少。免疫组织化学显示 JMJD8 在未损伤的小鼠中与 GFAP 共标记。脊髓背角星形胶质细胞中 JMJD8 的敲低诱导痛觉行为。进一步的研究表明，脊髓背角星形胶质细胞中 JMJD8 的过表达不仅逆转了痛觉行为，而且还激活了脊髓背角 A1 星形胶质细胞。这些结果表明，JMJD8 可能通过影响激活的脊髓背角 A1 星形胶质细胞来调节痛觉敏感性，并且可能是 NP 的潜在治疗靶点。
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