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MicroRNA-144 relieves chronic constriction injury-induced neuropathic pain via targeting RASA1.
Biotechnology and Applied Biochemistry ( IF 3.2 ) Pub Date : 2019-11-18 , DOI: 10.1002/bab.1854
Xianjie Zhang 1 , Hongli Guo 2 , An Xie 1 , Ou Liao 1 , Feng Ju 1 , YuKai Zhou 1
Affiliation  

MicroRNAs (miRNAs) have been shown to participate in development of neuropathic pain. However, the role of microRNA‐144 (miR‐144) in neuropathic pain remains unclear. In the present study, we established a neuropathic pain mouse model via chronic constriction injury (CCI)‐induction. The successful establishment of this model was confirmed via evaluation of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). By using this model, we found that miR‐144 was significantly downregulated in CCI‐induced neuropathic pain mice. In addition, intrathecal injection of miR‐144 agomiR alleviated mechanical and thermal hyperalgesia in neuropathic pain mice as shown by the increased of PWT and PWL. Moreover, miR‐144 negatively regulated neuroinflammation by decreasing the expression of proinflammatory mediators, including TNF‐α (tumor necrosis factor‐α), IL (interleukin)‐1β, and IL‐6, thus facilitating the inhibition of neuropathic pain development. Mechanistically, RASA1 (RAS P21 Protein Activator 1) was downregulated following the injection of agomiR‐144, and was verified to be a target of miR‐144. Furthermore, overexpression of RASA1 reversed the inhibitory effect of miR‐144 on neuropathic pain. Therefore, the present study suggested that miR‐144 has the potential to be explored as therapeutic target for treatment of neuropathic pain.

中文翻译:

MicroRNA-144通过靶向RASA1缓解慢性收缩损伤引起的神经性疼痛。

MicroRNA(miRNA)已显示参与神经性疼痛的发展。但是,microRNA-144(miR-144)在神经性疼痛中的作用仍不清楚。在本研究中,我们通过慢性收缩损伤(CCI)诱导建立了神经性疼痛小鼠模型。通过评估缩爪阈值(PWT)和缩爪潜伏期(PWL)证实了该模型的成功建立。通过使用该模型,我们发现在CCI诱导的神经性疼痛小鼠中miR-144明显下调。此外,鞘内注射miR-144 agomiR可减轻神经性疼痛小鼠的机械和热痛觉过敏,如PWT和PWL的增加所表明。此外,miR-144通过降低促炎性介质的表达来负调控神经炎症,包括TNF-α(肿瘤坏死因子-α),IL(白介素)-1β和IL-6,从而有助于抑制神经性疼痛的发展。从机理上讲,在注射agomiR-144之后,RASA1(RAS P21蛋白激活剂1)被下调,并被证实是miR-144的靶标。此外,RASA1的过表达逆转了miR-144对神经性疼痛的抑制作用。因此,本研究表明,miR-144有潜力被探索为治疗神经性疼痛的治疗靶标。RASA1的过表达逆转了miR-144对神经性疼痛的抑制作用。因此,本研究表明,miR-144有潜力被探索为治疗神经性疼痛的治疗靶标。RASA1的过表达逆转了miR-144对神经性疼痛的抑制作用。因此,本研究表明,miR-144有潜力被探索为治疗神经性疼痛的治疗靶标。
更新日期:2019-11-18
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