LncRNA uc.48+is involved in diabetic neuropathic pain mediated by the P2X3 receptor in the dorsal root ganglia
LncRNA uc.48+is involved in diabetic neuropathic pain mediated by the P2X3 receptor in the dorsal root ganglia
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LncRNA uc.48 参与背根神经节 P2X(3) 受体介导的糖尿病神经性疼痛
DOI：
10.1007/s11302-015-9488-x
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发表时间：
2016-03-01
影响因子：
3.5
通讯作者：
Liang, Shangdong
中科院分区：
文献类型：
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作者：
Wang, Shouyu;Xu, Hong;Liang, Shangdong
一些长的非编码RNA(LncRNAs)参与维持细胞和组织内稳态的生理过程，因此，LncRNAs的异常表达参与了许多病理疾病的发生和发展。研究表明，小鼠体内某些lncRNAs的基因敲除会导致围生期或出生后死亡或发育缺陷。糖尿病(DM)是周围神经病变的主要原因。我们的研究表明，LncRNA uc.48+在糖尿病大鼠背根神经节(DRG)和糖尿病患者血清标本中的表达水平增加。提示lncRNA uc.48+参与了糖尿病的病理生理过程。本研究的目的是探讨LncRNAuc.48+小干扰RNA(SiRNA)对背根节P2X(3)受体介导的糖尿病神经病理性疼痛(DNP)的影响。机械戒断阈值(MWT)和热戒断潜伏期(TWL)分别采用von Frey检验和Hargreaves检验。逆转录-聚合酶链式反应(RT-PCR)、免疫组织化学和Western blotting检测DRG中P2X(3)蛋白和信使RNA(MRNA)的表达。实验结果表明，糖尿病大鼠的MWT和TWL值均低于正常对照组。经lncRNAuc.48+siRNA治疗的DM大鼠的MWT和TWL值均高于DM大鼠，但DM大鼠组和DM+scurble siRNA组之间无显著差异。糖尿病大鼠背根神经节中P2X(3)蛋白和mRNA的表达水平高于对照组，而uc.48+siRNA治疗组大鼠背根神经节中的P2X(3)蛋白和mRNA的表达水平明显低于DM大鼠。与糖尿病组相比，uc.48+siRNA治疗组大鼠背根神经节中肿瘤坏死因子-α的表达水平显著降低。Uc.48+siRNA处理后，DM DRG中ERK1/2的磷酸化和活化程度降低。因此，uc.48+siRNA治疗可能通过抑制DRG中P2X(3)受体介导的兴奋性传递而减轻DNP。
Some long non-coding RNAs (lncRNAs) participate in physiological processes that maintain cellular and tissue homeostasis, and thus, the dysregulated expression of lncRNAs is involved in the onset and progression of many pathological conditions. Research has indicated that the genetic knockout of some lncRNAs in mice resulted in peri- or postnatal lethality or developmental defects. Diabetes mellitus (DM) is a major cause of peripheral neuropathy. Our studies showed that the expression levels of lncRNA uc.48+ in the diabetic rat dorsal root ganglia (DRG) and the DM patients' serum samples were increased. It suggested that lncRNA uc.48+ was involved in the pathophysiological process of DM. The aim of this study was to investigate the effects of lncRNA uc.48+ small interfering RNA (siRNA) on diabetic neuropathic pain (DNP) mediated by the P2X(3) receptor in the DRG. The values of the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured by the von Frey test and Hargreaves' test, respectively. The levels of P2X(3) protein and messenger RNA (mRNA) in the DRG were detected by reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, and western blotting. The experiments showed that the MWT and TWL values in DM rats were lower than those in the control rats. The MWT and TWL values in DM rats treated with lncRNA uc.48+ siRNA were increased compared to those in DM rats, but there was no significant difference between the DM rat group and the DM + scramble siRNA group. The levels of P2X(3) protein and mRNA in the DM DRG were higher than those in the control, while the levels of P2X(3) protein and mRNA in the DG of DM rats treated with uc.48+ siRNA were significantly decreased compared to those in DM rats. The expression levels of TNF-alpha in the DRG of DM rats treated with uc.48+ siRNA were significantly decreased compared to those in the DM group. The phosphorylation and activation of ERK1/2 in the DM DRG were decreased by uc.48+ siRNA treatment. Therefore, uc.48+ siRNA treatment may alleviate the DNP by inhibiting the excitatory transmission mediated by the P2X(3) receptor in DRG.