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微小RNA-142-3p是脊髓损伤感觉功能恢复的潜在治疗靶点。

miR-142-3p is a Potential Therapeutic Target for Sensory Function Recovery of Spinal Cord Injury.

作者信息

Wang Tianyi, Yuan Wenqi, Liu Yong, Zhang Yanjun, Wang Zhijie, Chen Xueming, Feng Shiqing, Xiu Yucai, Li Wenhua

机构信息

Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China (mainland).

Department of Pediatric Internal Medicine, Affiliated Hospital of Chengde Medical College, Chengde, Hebei, China (mainland).

出版信息

Med Sci Monit. 2015 Aug 28;21:2553-6. doi: 10.12659/MSM.894098.

Abstract

Spinal cord injury (SCI), which is a leading cause of disability in modern society, commonly results from trauma. It has been reported that application of sciatic nerve conditioning injury plays a positive role in repairing the injury of the ascending spinal sensory pathway in laboratory animals. Because of the complexity of SCI and related ethics challenges, sciatic nerve conditioning injury cannot be applied in clinical therapy. Accordingly, it is extremely important to study its mechanism and develop replacement therapy. Based on empirical study and clinical trials, this article suggests that miR-142-3p is the key therapeutic target for repairing sensory function, based on the following evidence. Firstly, studies have reported that endogenous cAMP is the upstream regulator of 3 signal pathways that are partially involved in the mechanisms of sciatic nerve conditioning injury, promoting neurite growth. The regulated miR-142-3p can induce cAMP elevation via adenylyl cyclase 9 (AC9), which is abundant in dorsal root ganglia (DRG). Secondly, compared with gene expression regulation in the injured spinal cord, inhibition of microRNA (miRNA) in DRG is less likely to cause trauma and infection. Thirdly, evidence of miRNAs as biomarkers and therapeutic targets in many diseases has been reported. In this article we suggest, for the first time, imitating sciatic nerve conditioning injury, thereby enhancing central regeneration of primary sensory neurons via interfering with the congenerous upstream regulator AC9 of the 3 above-mentioned signal pathways. We hope to provide a new clinical treatment strategy for the recovery of sensory function in SCI patients.

摘要

脊髓损伤(SCI)是现代社会导致残疾的主要原因之一,通常由外伤引起。据报道,坐骨神经预处理损伤在实验动物的脊髓感觉上行通路损伤修复中发挥积极作用。由于脊髓损伤的复杂性以及相关伦理挑战,坐骨神经预处理损伤无法应用于临床治疗。因此,研究其机制并开发替代疗法极为重要。基于实证研究和临床试验,本文提出miR-142-3p是修复感觉功能的关键治疗靶点,依据如下证据。首先,研究报道内源性环磷酸腺苷(cAMP)是部分参与坐骨神经预处理损伤机制的3条信号通路的上游调节因子,可促进神经突生长。受调控的miR-142-3p可通过在背根神经节(DRG)中大量存在的腺苷酸环化酶9(AC9)诱导cAMP升高。其次,与损伤脊髓中的基因表达调控相比,抑制背根神经节中的微小RNA(miRNA)引发创伤和感染的可能性较小。第三,已有报道称miRNA在多种疾病中作为生物标志物和治疗靶点的证据。在本文中,我们首次提出模仿坐骨神经预处理损伤,从而通过干扰上述3条信号通路的同源上游调节因子AC9来增强初级感觉神经元的中枢再生。我们希望为脊髓损伤患者感觉功能的恢复提供一种新的临床治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c9c/4557393/4f52aefa0835/medscimonit-21-2553-g001.jpg

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