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微小RNA-34a通过抑制高迁移率族蛋白B1,经由Toll样受体4信号通路减轻脊髓损伤。

miR-34a alleviates spinal cord injury via TLR4 signaling by inhibiting HMGB-1.

作者信息

Zhou Jianmin, Shuang Ou, Li Jian, Cai Zijun, Wu Chong, Wang Wenyu

机构信息

Department of Orthopedics, Shangrao People's Hospital, Shangrao, Jiangxi 334000, P.R. China.

出版信息

Exp Ther Med. 2019 Mar;17(3):1912-1918. doi: 10.3892/etm.2018.7102. Epub 2018 Dec 17.

Abstract

The aim of the present study was to investigate the effect of microRNA (miR)-34a on spinal cord injury (SCI)-induced inflammation and the possible underlying mechanisms. The results indicated that miR-34a expression was downregulated in a rat model of SCI compared with the control group. Furthermore, miR-34a knockdown was demonstrated to aggravate inflammation, inhibit cell proliferation and enhance apoptosis in an model of SCI. MiR-34a inhibition was demonstrated to upregulate the expression of inducible nitric oxide synthase and nitric oxide, as well as inducing the expression of toll-like receptor 4 (TLR4) and high mobility group box-1 (HMGB-1) in an model of SCI. TLR4 inhibitor reduced the effects of miR-34a downregulation on inflammation and cell growth in SCI. Together, these results suggest that miR-34a is able to alleviate SCI via inhibiting HMGB-1 expression in TLR4 signaling.

摘要

本研究的目的是探讨微小RNA(miR)-34a对脊髓损伤(SCI)诱导的炎症的影响及其潜在机制。结果表明,与对照组相比,miR-34a在SCI大鼠模型中的表达下调。此外,在SCI模型中,miR-34a基因敲低被证明会加重炎症、抑制细胞增殖并增强细胞凋亡。在SCI模型中,miR-34a抑制被证明会上调诱导型一氧化氮合酶和一氧化氮的表达,以及诱导Toll样受体4(TLR4)和高迁移率族蛋白B1(HMGB-1)的表达。TLR4抑制剂可降低miR-34a下调对SCI炎症和细胞生长的影响。这些结果共同表明,miR-34a能够通过抑制TLR4信号通路中的HMGB-1表达来减轻SCI。

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