MicroRNA-146a Contributes to SCI Recovery via Regulating TRAF6 and IRAK1 Expression.

MicroRNA-146a Contributes to SCI Recovery via Regulating TRAF6 and IRAK1 Expression.
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MicroRNA-146a 通过调节 TRAF6 和 IRAK1 表达促进 SCI 恢复。

DOI:
10.1155/2016/4013487
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发表时间:
2016
影响因子:
--
通讯作者:
Lin H
Lin H
中科院分区:
生物学3区
文献类型:
--
作者:
Wei J;Wang J;Zhou Y;Yan S;Li K;Lin H

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MicroRNA-146a 参与脊髓损伤 (SCI) 恢复。直到最近,miRNA-146a 如何参与 SCI 仍不清楚。在本研究中,我们试图利用大鼠模型探讨 miRNA-146a 在 SCI 恢复中的作用。直到术后7天,测量三组(假手术组、SCI组和miRNA-146a antagomir注射组)的miRNA-146a可能靶基因(包括IRAK1和TARF6)以及促炎细胞因子的表达。此外,在整个实验过程中,使用 Basso Beattie Bresnahan (BBB) 来估计动物的动机。进行荧光素酶测定以证明 miRNA-146a 可以直接靶向 IRAK1 和 TRAF6 的 mRNA。我们的实验表明,在 SCI 模型中,miRNA-146a 通过抑制 IRAK1 和 TRAF6 的表达来抑制促炎细胞因子的分泌。相反,miRNA-146a 可能通过脊髓中的 IRAK1/TRAF6 通路被炎症介质上调。作为负反馈元件,miRNA-146a可以确保IRAK1和TRAF6介导的基因的表达受到严格控制。因此,miRNA-146a可能作为SCI干预的新治疗靶点。
MicroRNA-146a participates in spinal cord injury (SCI) recovery. Until recently, how miRNA-146a participates in SCI remained unclear. In this study, we tried to explore the roles of miRNA-146a in the recovery of SCI using a rat model. The expression of the probable target genes of miRNA-146a (including IRAK1 and TARF6) as well as proinflammation cytokines were measured until 7 days after surgery in the three groups (sham group, SCI group, and miRNA-146a antagomir injection group). Also, the animals' motivations were estimated using Basso Beattie Bresnahan (BBB) during the whole experiment. A luciferase assay was performed to demonstrate that miRNA-146a could directly target the mRNAs of IRAK1 and TRAF6. Our experiments indicate that miRNA-146a inhibits proinflammatory cytokine secretion by suppressing IRAK1 and TRAF6 expression in the SCI model. In contrast, miRNA-146a may be upregulated by inflammatory mediators via the IRAK1/TRAF6 pathway in the spinal cord. As a negative feedback element, miRNA-146a could make sure that the expression of IRAK1- and TRAF6-mediated genes was under tight control. Thus, miRNA-146a may serve as a novel therapeutic target for SCI interventions.
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