MicroRNA cluster miR-17-92 regulates multiple functionally related voltage-gated potassium channels in chronic neuropathic pain.
MicroRNA cluster miR-17-92 regulates multiple functionally related voltage-gated potassium channels in chronic neuropathic pain.
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DOI：
10.1038/ncomms16079
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发表时间：
2017-07-05
影响因子：
16.6
通讯作者：
Suzuki H
中科院分区：
文献类型：
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作者：
Sakai A;Saitow F;Maruyama M;Miyake N;Miyake K;Shimada T;Okada T;Suzuki H
miR-17-92是一个由6个不同成员组成的microRNA簇。在这里，我们表明miR-17-92簇及其单个成员调节慢性神经性疼痛。神经损伤后初级感觉神经元中所有簇成员持续上调。miR-18 a、miR-19 a、miR-19 b和miR-92 a簇成员的过表达在大鼠中诱发机械性异常性疼痛，而它们的阻断在神经性疼痛的大鼠模型中诱发机械性异常性疼痛。miR-17-92簇的合理靶点包括编码许多电压门控钾通道及其调节亚基的基因。单细胞分析揭示了miR-17-92簇及其预测的靶点在初级感觉神经元中的广泛共表达。miR-17-92下调钾通道的表达，并减少外向钾电流，特别是A型电流。钾通道调节剂的联合应用协同减轻了由神经损伤或miR-17-92过表达诱导的机械性异常性疼痛。miR-17-92簇似乎协同调节多个电压门控钾通道亚基的功能，使机械性异常性疼痛持续存在。电压门控钾通道的失调是神经病理性疼痛的特征。在大鼠模型中，作者鉴定了microRNA簇miR-17-92作为背根神经节神经元中电压门控钾通道的调节剂。
miR-17-92 is a microRNA cluster with six distinct members. Here, we show that the miR-17-92 cluster and its individual members modulate chronic neuropathic pain. All cluster members are persistently upregulated in primary sensory neurons after nerve injury. Overexpression of miR-18a, miR-19a, miR-19b and miR-92a cluster members elicits mechanical allodynia in rats, while their blockade alleviates mechanical allodynia in a rat model of neuropathic pain. Plausible targets for the miR-17-92 cluster include genes encoding numerous voltage-gated potassium channels and their modulatory subunits. Single-cell analysis reveals extensive co-expression of miR-17-92 cluster and its predicted targets in primary sensory neurons. miR-17-92 downregulates the expression of potassium channels, and reduced outward potassium currents, in particular A-type currents. Combined application of potassium channel modulators synergistically alleviates mechanical allodynia induced by nerve injury or miR-17-92 overexpression. miR-17-92 cluster appears to cooperatively regulate the function of multiple voltage-gated potassium channel subunits, perpetuating mechanical allodynia. Dysregulation of voltage gated potassium channels is a feature of neuropathic pain. Here in a rat model the authors identify the microRNA cluster miR-17-92 as a regulator of voltage gated potassium channels in the dorsal root ganglion neurons.
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影响因子：
11.2
作者：
Noro, T;Miyake, K;Shimada, T
通讯作者：
Shimada, T
影响因子：
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通讯作者：
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