Elevated microRNA-129-5p level ameliorates neuroinflammation and blood-spinal cord barrier damage after ischemia-reperfusion by inhibiting HMGB1 and the TLR3-cytokine pathway.
Elevated microRNA-129-5p level ameliorates neuroinflammation and blood-spinal cord barrier damage after ischemia-reperfusion by inhibiting HMGB1 and the TLR3-cytokine pathway.
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升高的 microRNA-129-5p 水平可通过抑制 HMGB1 和 TLR3 细胞因子途径改善缺血再灌注后的神经炎症和血脊髓屏障损伤。
DOI：
10.1186/s12974-017-0977-4
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发表时间：
2017-10-23
影响因子：
9.3
通讯作者：
Ma H
中科院分区：
文献类型：
--
作者：
Li XQ;Chen FS;Tan WF;Fang B;Zhang ZL;Ma H
缺血-再灌注（IR）影响microRNA（miR）表达并引起大量炎症。肿瘤抑制剂miR-129- 5 p在脑IR中的多种作用最近已被报道，但其在脊髓中的功能尚不清楚。在此，我们研究了miR-129- 5 p在脊髓IR后的作用，特别是在调节高迁移率族蛋白1（HMGB 1）和Toll样受体（TLR）-3通路中的作用。通过阻断主动脉弓5分钟诱导缺血，通过RT-PCR、蛋白质印迹和荧光素酶分析阐明miR-129- 5 p和HMGB 1之间的关系。通过双重免疫荧光法测定HMGB 1的细胞分布。使用合成miR、rHMGB 1和TLR 3激动剂Poly（I：C）评估miR-129- 5 p对HMGB 1、TLR 3和下游细胞因子表达的影响。通过测定伊文思蓝（EB）染料外渗和含水量来检查血脊髓屏障（BSCB）通透性。时间miR-129- 5 p和HMGB 1表达谱和荧光素酶测定结果表明miR-129- 5 p靶向HMGB 1。与Sham组相比，IR组HMGB 1免疫反应阳性率明显增高，主要分布于神经元和小胶质细胞。鞘内注射miR-129- 5 p模拟物可显著降低HMGB 1、TLR 3、白细胞介素（IL）-1β和肿瘤坏死因子（TNF）-α水平以及术后48 h的双标记细胞计数，而rHMGB 1和Poly（I：C）可逆转这些效应。注射miR-129- 5 p模拟物可保留运动功能并防止BSCB渗漏，因为Basso小鼠量表评分增加，EB渗出和含水量减少，而注射rHMGB 1和Poly（I：C）则会加剧这些损伤。增加miR-129- 5 p水平通过抑制HMGB 1和TLR 3相关细胞因子改善炎症诱导的神经元和BCSB损伤来保护IR。
Ischemia-reperfusion (IR) affects microRNA (miR) expression and causes substantial inflammation. Multiple roles of the tumor suppressor miR-129-5p in cerebral IR have recently been reported, but its functions in the spinal cord are unclear. Here, we investigated the role of miR-129-5p after spinal cord IR, particularly in regulating high-mobility group box-1 (HMGB1) and the Toll-like receptor (TLR)-3 pathway. Ischemia was induced via 5-min occlusion of the aortic arch. The relationship between miR-129-5p and HMGB1 was elucidated via RT-PCR, western blotting, and luciferase assays. The cellular distribution of HMGB1 was determined via double immunofluorescence. The effect of miR-129-5p on the expression of HMGB1, TLR3, and downstream cytokines was evaluated using synthetic miRs, rHMGB1, and the TLR3 agonist Poly(I:C). Blood-spinal cord barrier (BSCB) permeability was examined by measuring Evans blue (EB) dye extravasation and the water content. The temporal miR-129-5p and HMGB1 expression profiles and luciferase assay results indicated that miR-129-5p targeted HMGB1. Compared with the Sham group, the IR group had higher HMGB1 immunoreactivity, which was primarily distributed in neurons and microglia. Intrathecal injection of the miR-129-5p mimic significantly decreased the HMGB1, TLR3, interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels and the double-labeled cell count 48 h post-surgery, whereas rHMGB1 and Poly(I:C) reversed these effects. Injection of miR-129-5p mimic preserved motor function and prevented BSCB leakage based on increased Basso Mouse Scale scores and decreased EB extravasation and water content, whereas injection rHMGB1 and Poly(I:C) aggravated these injuries. Increasing miR-129-5p levels protect against IR by ameliorating inflammation-induced neuronal and BCSB damage by inhibiting HMGB1 and TLR3-associated cytokines.
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影响因子：
9.3
作者：
Li XQ;Lv HW;Tan WF;Fang B;Wang H;Ma H
通讯作者：
Ma H
影响因子：
9.3
作者：
Li XQ;Lv HW;Wang ZL;Tan WF;Fang B;Ma H
通讯作者：
Ma H
影响因子：
8.8
作者：
Das N;Dewan V;Grace PM;Gunn RJ;Tamura R;Tzarum N;Watkins LR;Wilson IA;Yin H
通讯作者：
Yin H
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
LncRNA CRNDE 通过 TLR3-NF-B-细胞因子信号通路触发炎症
影响因子：
--
作者：
Li, Haowen;Li, Qi;Wang, Yajie
通讯作者：
Wang, Yajie