Role of MicroRNA-143 in Nerve Injury-Induced Upregulation of Dnmt3a Expression in Primary Sensory Neurons.
Role of MicroRNA-143 in Nerve Injury-Induced Upregulation of Dnmt3a Expression in Primary Sensory Neurons.
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microRNA-143在神经损伤诱导的初级感觉神经元Dnmt3a表达上调中的作用
DOI：
10.3389/fnmol.2017.00350
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发表时间：
2017
影响因子：
4.8
通讯作者：
Tao YX
中科院分区：
文献类型：
--
作者：
Xu B;Cao J;Zhang J;Jia S;Wu S;Mo K;Wei G;Liang L;Miao X;Bekker A;Tao YX
周围神经损伤后，背根神经节（DRG）DNA甲基转移酶3A（Dnmt 3a）mRNA及其编码蛋白的表达增加。这种增加被认为是通过损伤的背根神经节中疼痛相关基因（例如Oprm 1）的表观遗传沉默而导致神经性疼痛发生的内源性诱发因素。然而，周围神经损伤后DRG DNMT 3a如何增加仍然是难以捉摸的。我们在这里报道了由第五脊神经结扎（SNL）引起的周围神经损伤下调损伤DRG中microRNA（miR）-143的表达。这种下调是SNL诱导的DRG Dnmt 3a增加所需的，因为通过将miR-143模拟物显微注射到损伤的DRG中来挽救miR-143下调阻断了SNL诱导的Dnmt 3a增加，并恢复了SNL诱导的损伤的DRG中Oprm 1 mRNA及其编码μ阿片受体（莫尔）的减少，损害了脊髓中枢敏化和神经性疼痛，并改善了SNL后的吗啡镇痛作用。通过在未处理大鼠的DRG中显微注射miR-143抑制剂来模拟SNL诱导的DRG miR-143下调，在注射的DRG中增加了Dnmt 3a的表达，降低了Oprm 1 mRNA和莫尔的表达，并产生神经病理性疼痛样症状。这些发现表明，miR-143是神经性疼痛条件下DRG中Dnmt 3a表达的负调节因子，并且可能是神经性疼痛治疗管理的潜在靶标。
Peripheral nerve injury increased the expression of the DNA methyltransferase 3A (Dnmt3a) mRNA and its encoding Dnmt3a protein in injured dorsal root ganglia (DRG). This increase is considered as an endogenous instigator in neuropathic pain genesis through epigenetic silencing of pain-associated genes (such as Oprm1) in injured DRG. However, how DRG DNMT3a is increased following peripheral nerve injury is still elusive. We reported here that peripheral nerve injury caused by the fifth spinal nerve ligation (SNL) downregulated microRNA (miR)-143 expression in injured DRG. This downregulation was required for SNL-induced DRG Dnmt3a increase as rescuing miR-143 downregulation through microinjection of miR-143 mimics into injured DRG blocked the SNL-induced increase in Dnmt3a and restored the SNL-induced decreases in Oprm1 mRNA and its encoding mu opioid receptor (MOR) in injured DRG, impaired spinal cord central sensitization and neuropathic pain, and improved morphine analgesic effects following SNL. Mimicking SNL-induced DRG miR-143 downregulation through DRG microinjection of miR143 inhibitors in naive rats increased the expression of Dnmt3a and reduced the expression of Oprm1 mRNA and MOR in injected DRG and produced neuropathic pain-like symptoms. These findings suggest that miR-143 is a negative regulator in Dnmt3a expression in the DRG under neuropathic pain conditions and may be a potential target for therapeutic management of neuropathic pain.
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影响因子：
16.2
作者：
Cui, Lian;Miao, Xuerong;Liang, Lingli;Abdus-Saboor, Ishmail;Olson, William;Fleming, Michael S.;Ma, Minghong;Tao, Yuan-Xiang;Luo, Wenqin
通讯作者：
Luo, Wenqin
影响因子：
3.3
作者：
Fan L;Guan X;Wang W;Zhao JY;Zhang H;Tiwari V;Hoffman PN;Li M;Tao YX
通讯作者：
Tao YX
影响因子：
82.9
作者：
Kawasaki, Yasuhiko;Xu, Zhen-Zhong;Ji, Ru-Rong
通讯作者：
Ji, Ru-Rong
影响因子：
3.3
作者：
Liang L;Zhao JY;Gu X;Wu S;Mo K;Xiong M;Marie Lutz B;Bekker A;Tao YX
通讯作者：
Tao YX
DOI：
10.1124/jpet.103.060582
发表时间：
2004-04-01
影响因子：
3.5
作者：
Rashid, MH;Inoue, M;Ueda, H
通讯作者：
Ueda, H