miRNA-155 silencing reduces sciatic nerve injury in diabetic peripheral neuropathy
miRNA-155 silencing reduces sciatic nerve injury in diabetic peripheral neuropathy
复制标题
microRNA-155沉默可减少糖尿病周围神经病变的坐骨神经损伤
DOI：
10.1530/jme-19-0067
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发表时间：
2019-10-01
影响因子：
3.5
通讯作者：
Yang, Fengrui
中科院分区：
文献类型：
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作者：
Chen, Ji;Li, Chao;Yang, Fengrui
神经性疼痛是糖尿病（DM）最常见的并发症之一，影响生活质量。越来越多的研究强调了miRNA在DM中的作用。因此，本研究旨在研究miR-155在糖尿病周围神经病变（DPN）中的作用。用5.5mM葡萄糖处理大鼠雪旺细胞（SC）建立体外DPN模型。进行功能获得或丧失研究以确定miR-155对Nrf 2、细胞功能、活性氧和炎症的影响。采用链脲佐菌素注射和坐骨神经损伤建立DNP大鼠模型。接下来，使用miR-155阿克罗米或阿戈米来研究与miR-155相关的对运动和坐骨神经传导速度（MNCV，SNCV）、血管生成和体内炎症反应的影响。通过双荧光素酶报告基因分析确定Nrf 2是miR-155的靶点。沉默miR-155或恢复Nrf 2在体外促进细胞增殖、抑制细胞凋亡并减轻炎症。miR-155对DPN大鼠MNCV和SNCV的抑制作用增强，血管生成增强，炎症减轻。此外，当Nrf 2在体外和体内恢复时，miR-155所发挥的作用被逆转。总之，我们研究的关键发现提供了证据表明miR-155靶向并抑制DPN中的Nrf 2。发现miR-155沉默可以减轻DPN中的坐骨神经损伤，突出了其作为DPN治疗靶点的潜力。
Neuropathic pain represents one of the most common complications associated with diabetes mellitus (DM) that impacts quality of life. Accumulating studies have highlighted the involvement of miRNAs in DM. Thus, the current study aimed to investigate the roles of miR-155 in diabetic peripheral neuropathy (DPN). In vitro DPN models were established using rat Schwann cells (SCs) by treatment with 5.5 mM glucose. Gain- or loss-of-function studies were conducted to determine the effect of miR-155 on Nrf2, cellular function, reactive oxygen species and inflammation. Rat DNP models were established by streptozotocin injection and damage of sciatic nerve. Next, miR-155 antagomir or agomir was employed to investigate the effects associated with miR-155 on motor and sciatic nerve conduction velocity (MNCV, SNCV), angiogenesis and inflammatory response in vivo. Nrf2 was identified to be a target of miR-155 by dual-luciferase reporter gene assay. Silencing of miR-155 or restoration of Nrf2 promoted cell proliferation, inhibited apoptosis and alleviated inflammation in vitro. miR-155 antagomir-induced inhibition increased MNCV and SNCV, strengthened angiogenesis and alleviated inflammation in DPN rats. Additionally, the effects exerted by miR-155 were reversed when Nrf2 was restored both in vitro and in vivo. Taken together, the key findings of our study provide evidence indicating that miR-155 targeted and suppressed Nrf2 in DPN. miR-155 silencing was found to alleviate sciatic nerve injury in DPN, highlighting its potential as a therapeutic target for DPN.