LncRNA uc.48+ is involved in diabetic neuropathic pain mediated by the P2X sub(3) receptor in the dorsal root ganglia

• Published in: Purinergic signalling 2016-03, Vol.12 (1), p.139-148
• Main Authors: Wang, Shouyu, Xu, Hong, Zou, Lifang, Xie, Jinyang, Wu, Hong, Wu, Bing, Yi, Zhihua, Lv, Qiulan, Zhang, Xi, Ying, Mofeng, Liu, Shuangmei, Li, Guilin, Gao, Yun, Xu, Changshui, Zhang, Chunping, Xue, Yun, Liang, Shangdong
• Format: Article
• Language: English
• ISSN: 1573-9538; 1573-9546
• DOI: 10.1007/s11302-015-9488-x

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 sub(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 sub(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 sub(3) protein and mRNA in the DM DRG were higher than those in the control, while the levels of P2X sub(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 sub(3) receptor in DRG.