Downregulation of miR-199b promotes the acute spinal cord injury through IKKβ-NF-κB signaling pathway activating microglial cells

被引：65

作者：

Zhou, Heng-Jun ^{[1
]}

Wang, Li-Qing ^{[2
]}

Xu, Qing-Sheng ^{[1
]}

Fan, Zuo-Xu ^{[1
]}

Zhu, Yu ^{[1
]}

Jiang, Hao ^{[1
]}

Zheng, Xiu-Jue ^{[1
]}

Ma, Yue-Hui ^{[1
]}

Zhan, Ren-Ya ^{[1
]}

机构：

[1] Zhejiang Univ, Affiliated Hosp 1, Dept Neurosurg, 79 Qingchun Rd, Hangzhou 310003, Zhejiang, Peoples R China

[2] Zhejiang Univ, Affiliated Hosp 1, Dept Anesthesia, Hangzhou 310003, Zhejiang, Peoples R China

来源：

EXPERIMENTAL CELL RESEARCH | 2016年 / 349卷 / 01期

基金：

中国国家自然科学基金;

关键词：

MiR-199b; Microglia; Spinal cord injury; IKK beta-NF-kappa B signaling pathway; MESENCHYMAL STEM-CELLS; TUMOR-NECROSIS-FACTOR; EXPRESSION; APOPTOSIS; INFLAMMATION; SURVIVAL; NEURONS; MODEL; RATS;

D O I：

10.1016/j.yexcr.2016.09.020

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Inflammatory response played an important role in the progression of spinal cord injury (SCI). Several miRNAs were associated with the pathology of SCI. However, the molecular mechanism of miRNA involving in inflammatory response in acute SCI (ASCI) was poorly understood. Sprague-Dawley (SD) rats were divided into 2 groups: control group (n=6) and acute SCI (ASCI) group (n=6). The expression of miR-199b and NB kinase ()nuclear factor-kappa B (IKK beta-NF-kappa B) signaling pathway were evaluated by quantitative reverse transcriptionPCR (qRT-PCR) in rats with ASCI and in primary microglia activated by lipopolysaccharide (LPS). We found that downregulation of miR-199b and activation of 1KK beta-NF-kappa B were observed in rats after ASCI and in activated microglia. miR-199b negatively regulated IKK beta by targeting its 3'- untranslated regions (UTR) through using luciferase reporter assay. Overexpression of miR-199b reversed the up-regulation of IKK beta, p-p65, tumor necrosis factor-a (TNF-alpha) and interleukin-1 beta (IL-beta) in LPS-treated BV2 cells assessed by western blotting analysis. In addition, BMS-345541 reversed the up-regulation effects of miR-199b inhibitor on the expression of TNF-a and IL-1 beta. In the SCI rats, overexpression of miR-199b attenuated ASCI and decreased the expression of IKK beta-NF-kappa B signaling pathway and TNF-a and IL-1 beta. These results indicated that miR-199b attenuated ASCI at least partly through IKK beta-NF-kappa B signaling pathway and affecting the function of microglia. Our findings suggest that miR-199b may be employed as therapeutic for spinal cord injury.

引用

页码：60 / 67

页数：8

共 50 条

[31] S100A7 promotes the development of human endometriosis by activating NF-κB signaling pathway in endometrial stromal cells [J].

Sun, Qingqing ;

Cao, Yijuan ;

Lan, Yonglian ;

Lei, Lingling ;

Zhang, Bei ;

Wang, Shuyu .

CELL BIOLOGY INTERNATIONAL, 2021, 45 (06) :1327-1335

[32] HUCMSCs transplantation combined with ultrashort wave therapy attenuates neuroinflammation in spinal cord injury through NUR77/ NF-κB pathway [J].

Wang, Shuai ;

Jia, Yiying ;

Cao, Xiangyan ;

Feng, Sining ;

Na, Li ;

Dong, Hongxuan ;

Gao, Jian ;

Zhang, Lixin .

LIFE SCIENCES, 2021, 267

[33] MicroRNA-488 inhibits neural inflammation and apoptosis in spinal cord injury through restraint on the HMGB1/TLR4/NF-κB signaling pathway [J].

Niu, Feng ;

Pan, Shan .

NEUROREPORT, 2021, 32 (12) :1017-1026

[34] miR-423 Promotes Breast Cancer Invasion by Activating NF-κB Signaling [J].

Dai, Ting ;

Zhao, Xiaohui ;

Li, Yun ;

Yu, Lihong ;

Li, Yanan ;

Zhou, Xiang ;

Gong, Qing .

ONCOTARGETS AND THERAPY, 2020, 13 :5467-5478

[35] miR-136-5p Regulates the Inflammatory Response by Targeting the IKK/NF-B/A20 Pathway After Spinal Cord Injury [J].

Deng, Guiying ;

Gao, Yunbing ;

Cen, Zhongxi ;

He, Jichen ;

Cao, Baichuan ;

Zeng, Gaofeng ;

Zong, Shaohui .

CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2018, 50 (02) :512-524

[36] Tetramethylpyrazine inhibits the inflammatory response by downregulating the TNFR1/I κ B- α /NF- κ B p65 pathway after spinal cord injury [J].

Liu, Gang ;

Huo, Luyao ;

Deng, Bowen ;

Jiang, Shengyuan ;

Zhao, Yi ;

Mo, Yanjun ;

Bai, Huizhong ;

Xu, Lin ;

Hu, Chuanyu ;

Mu, Xiaohong .

TOXICOLOGY AND APPLIED PHARMACOLOGY, 2024, 484

[37] Resveratrol inhibits inflammation after spinal cord injury via SIRT-1/NF-κB signaling pathway [J].

Zhao, Haosen ;

Mei, Xifan ;

Yang, Dongfang ;

Tu, Guanjun .

NEUROSCIENCE LETTERS, 2021, 762

[38] Phillygenin inhibits neuroinflammation and promotes functional recovery after spinal cord injury via TLR4 inhibition of the NF-κB signaling pathway [J].

Zhang, Yu ;

Xiao, Shining ;

Dan, Fan ;

Yao, Geliang ;

Hong, Shu'e ;

Liu, Jiaming ;

Liu, Zhili .

JOURNAL OF ORTHOPAEDIC TRANSLATION, 2024, 48 :133-145

[39] MiR-543-5p inhibits inflammation and promotes nerve regeneration through inactivation of the NF-κB in rats after spinal cord injury [J].

Zhao, C-L. ;

Cui, H-A. ;

Zhang, X-R. .

EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES, 2019, 23 :39-46

[40] Brevilin A Ameliorates Acute Lung Injury and Inflammation Through Inhibition of NF-κB Signaling via Targeting IKKα/β [J].

Liu, Lu ;

Chen, Xian ;

Jiang, Yifang ;

Yuan, Yun ;

Yang, Luyao ;

Hu, Qiongying ;

Tang, Jianyuan ;

Meng, Xianli ;

Xie, Chunguang ;

Shen, Xiaofei .

FRONTIERS IN PHARMACOLOGY, 2022, 13

← 1 2 3 4 5 →