Increased ten-eleven translocation methylcytosine dioxygenase one in dorsal root ganglion contributes to inflammatory pain in CFA rats.
Increased ten-eleven translocation methylcytosine dioxygenase one in dorsal root ganglion contributes to inflammatory pain in CFA rats.
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背根神经节中 10-11 易位甲基胞嘧啶双加氧酶 1 的增加导致 CFA 大鼠的炎症性疼痛
DOI：
10.1177/17448069221143671
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发表时间：
2022-04
期刊：
影响因子：
3.3
通讯作者：
Xu, Guang-Yin
中科院分区：
文献类型：
--
作者：
Liu, Yun;Zhang, Ling;Xu, Zhen-hua;Zhu, Jie;Ma, Jia-ling;Gao, Yan-ping;Xu, Guang-Yin
关键词：
由泰特双加氧酶催化的DNA羟基化在哺乳动物神经元中大量发生。然而，10 - 11易位甲基胞嘧啶双加氧酶1（TET 1）的表达和羟甲基化状态对神经元损伤的影响尚不清楚。本研究旨在探讨TET 1和TET 2在完全弗氏佐剂（CFA）诱导的大鼠炎性痛中的表达。测定大鼠机械缩爪阈值（PWT）和热缩爪潜伏期（TWL），评价大鼠的疼痛行为。Western blotting法检测TET 1、TET 2在背根神经节（DRG）的表达。免疫荧光染色检测TRPV 1和TET 1的表达和共定位。鞘内注射Bobcat 339抑制背根神经节TET 1功能。注射CFA后大鼠的缩足阈和热缩足潜伏期明显缩短。Western blot结果显示，注射CFA后第3天TET 1的表达显著增加，TET 2的表达无统计学差异。免疫荧光结果显示TET 1与TRPV 1共定位。鞘内注射Bobcat 339可提高CFA大鼠的机械痛阈和热痛阈。我们的研究结果强调了TET 1在慢性炎症性疼痛模型中的作用。CFA大鼠TET 1表达增加，抑制TET 1表达可减轻炎症痛。
DNA hydroxylation catalyzed by Tet dioxygenases occurs abundantly in neurons in mammals. However, effects of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) expression and hydroxymethylation status on neuron injury remain unclear. This study was designed to explore the effects of TET1 and TET2 expression in the inflammatory pain of rats induced by complete Freund’s adjuvant (CFA). Mechanical paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL) were detected to assess pain behavior. The expression of TET1 and TET2 were measured in the dorsal root ganglion (DRG) with western blotting analysis. Immunofluorescence staining is employed to detect the expression and co-location of TRPV1 with TET1. Intrathecal administration of Bobcat339 was used to inhibit TET1 function in dorsal root ganglion. The paw withdrawal threshold and thermal withdrawal latency of rats were significantly reduced after CFA Injection. Western blot results showed that the expression of TET1 was significantly increased at 3 days after CFA injection, but TET2 had no statistical difference. Immunofluorescence results showed that TET1 was co-localized with TRPV1. Intrathecal administration of Bobcat339 improved mechanical and thermal pain threshold in CFA rats. Our findings highlight the role of TET1 in chronic inflammatory pain model. The expression of TET1 was increased in CFA rats, and suppression of TET1 will ameliorate inflammatory pain.
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