scholarly journals EZH2 Mediates miR-146a-5p/HIF-1α to Alleviate Inflammation and Glycolysis after Acute Spinal Cord Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Shuangfei Ni ◽  
Bo Yang ◽  
Lei Xia ◽  
Huafeng Zhang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cerebrospinal Fluid ◽  
Underlying Mechanism ◽  
Acute Spinal Cord Injury ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Expression Levels ◽  
Tnf Α ◽  
Cord Injury

Acute spinal cord injury (ASCI) is a severe traumatic disease of the central nervous system, the underlying mechanism of which is unclear. This study was intended to study the role of EZH2 and miR-146a-5p/HIF-1α in inflammation and glycolysis after ASCI, providing reference and basis for the clinical treatment and prognosis of ASCI injury. We used lipopolysaccharide (LPS) to induce inflammation of microglia, and we constructed the ASCI animal model. qRT-PCR detected the relative expression levels of EZH2, HIF-1α, miR-146a-5p, IL-6, TNF-α, IL-17, PKM2, GLUT1, and HK2 in cells and tissues. Western blot was performed to detect the expression levels of EZH2, HIF-1α, H3K27me3, IL-6, TNF-α, IL-17, PKM2, GLUT1, and HK2. ChIP verified the enrichment of H3K27me3 in the miR-146a-5p promoter region. Bioinformatics predicted the binding sites of HIF-1α and miR-146a-5p, and dual-luciferase reporter assay verified the binding of HIF-1α and miR-146a-5p. ELISA detects the levels of inflammatory factors IL-6, TNF-α, and IL-17 in the cerebrospinal fluid of rats. The GC-TOFMS was used to detect the changes of glycolytic metabolites in the cerebrospinal fluid of rats. EZH2 could mediate inflammation and glycolysis of microglia. EZH2 regulates inflammation and glycolysis through HIF-1α. EZH2 indirectly regulated the HIF-1α expression by mediating miR-146a-5p. EZH2 mediates miR-146a-5p/HIF-1α to alleviate inflammation and glycolysis in ASCI rats. In the present study, our results demonstrated that EZH2 could mediate miR-146a-5p/HIF-1α to alleviate the inflammation and glycolysis after ASCI. Therefore, EZH2/miR-146a-5p/HIF-1α might be a novel potential target for treating ASCI.

scholarly journals Zhenbao pill protects against acute spinal cord injury via miR-146a-5p regulating the expression of GPR17

2018 ◽  
Vol 38 (1) ◽  
Author(s):  
Yongxiong He ◽  
Bokang Lv ◽  
Yanqiang Huan ◽  
Bin Liu ◽  
Yutang Li ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Hind Limb ◽  
Neuronal Apoptosis ◽  
Acute Spinal Cord Injury ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Cord Injury

The aim of the present study was to observe the effect of zhenbao pill on the motor function of acute spinal cord injury (ASCI) rats and the molecular mechanisms involving miR-146a-5p and G-protein-coupled receptor 17 (GPR17). ASCI rat model was established by modified Allen method, and then the rats were divided into three groups. SH-SY5Y cells were cultured overnight in hypoxia condition and transfected with miR-146a-5p mimic or miR-146a-5p inhibitor. The hind limb motor function of the rats was evaluated by Basso, Beattie, Bresnahan (BBB) scoring system. Quantitative real-time PCR (qRT-PCR) and Western blot were used to detect the expression of miR-146a-5p, GPR17, inducible nitric oxide synthase (iNOS), interleukin 1β (IL-1β), and tumor necrosis factor α (TNF-α). Neuronal apoptosis was measured using flow cytometry assay. Luciferase reporter assay was performed to determine the regulation of miR-146a-5p on GPR17. Zhenbao pill could enhance hind limb motor function and attenuate the inflammatory response caused by ASCI. Moreover, zhenbao pill increased the level of miR-146a-5p and decreased GPR17 expression in vivo and in vitro. Bioinformatics software predicted that GPR17 3′-UTR had a binding site with miR-146a-5p. Luciferase reporter assay showed that miR-146a-5p had a negative regulatory effect on GPR17 expression. Knockdown of miR-146a-5p could reverse the effect of zhenbao pill on the up-regulation of GPR17 induced by hypoxia, reversed the inhibitory effect of zhenbao pill on the cell apoptosis induced by hypoxia and the recovery of zhenbao pill on hind limb motor function in ASCI rats. Zhenbao pill could inhibit neuronal apoptosis by regulating miR-146a-5p/GPR17 expression, and then promoting the recovery of spinal cord function.

scholarly journals miRNA-146a and miRNA-202-3p Attenuate Inflammatory Response by Inhibiting TLR4, IRAK1, and TRAF6 Expressions in Rats following Spinal Cord Injury

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Feng Sun ◽  
Haiwei Zhang ◽  
Jianhui Shi ◽  
Tianwen Huang ◽  
Yansong Wang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Rat Spinal Cord ◽  
Rat Serum ◽  
Inflammatory Reactions ◽  
Expression Levels ◽  
Tnf Α ◽  
Cord Injury ◽  
Anti Inflammatory

Spinal cord injury (SCI) is a catastrophic disease that induces a complex cascade of cellular reactions at the local lesion area, including secondary cell death and inflammatory reactions. Accumulating evidence has showed pro- and anti-inflammatory roles of microRNAs (miRNAs), a class of small RNAs, in SCI. The present study is aimed at investigating the effects of two miRNAs, miRNA-146a and miRNA-202-3p, on inflammatory response after SCI. Initially, we found that the expression levels of miRNA-146a and miRNA-202-3p were increased in the plasma samples of 32 SCI patients at days 3 and 7 after admission and the rat spinal cord at days 3 and 7 after SCI modeling compared with healthy controls and sham-operated rats, respectively. The expression levels of TLR4, IRAK1, and TRAF6 were declined in the rat spinal cord at days 1, 3, and 7 after SCI modeling compared with sham-operated rats. Injection of miRNA-146a mimic or miRNA-202-3p mimic decreased TLR4, IRAK1, and TRAF6 expressions in the rat spinal cord at days 1, 3, and 7 after SCI modeling, while injection of miRNA-146a antagomir or miRNA-202-3p antagomir produced opposed results. Subsequent results showed that the expression levels of tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and IL-8 were upregulated in the rat serum at days 1, 3, and 7 after SCI modeling compared with sham-operated rats. Injection of miRNA-146a mimic or miRNA-202-3p mimic decreased TNF-α, IL-1β, IL-6, and IL-8 expression levels in the rat serum at days 1, 3, and 7 after SCI modeling, while injection of miRNA-146a antagomir or miRNA-202-3p antagomir yielded opposed results. The expression levels of TNF-α, IL-1β, IL-6, and IL-8 were higher in the supernatants of PC12 cells transfected with anti-miRNA-146a or anti-miRNA-202-3p than in those transfected with si-TLR4, si-IRAK1, or si-TRAF6. These findings support the notion that miRNA-146a/miRNA-202-3p exerts anti-inflammatory functions after SCI.

Effect of Low-Level Laser Irradiation on Expression of TNF-α, IL-6 and IL-10 after Acute Spinal Cord Injury in Rats

2014 ◽  
Vol 41 (2) ◽  
pp. 0204003 ◽  
Author(s):  
王继猛 Wang Jimeng ◽  
梁卓文 Liang Zhuowen ◽  
胡学昱 Hu Xueyu ◽  
焦海斌 Jiao Haibin ◽  
王晶 Wang Jing ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Laser Irradiation ◽  
Acute Spinal Cord Injury ◽  
Low Level ◽  
Low Level Laser ◽  
Level Laser ◽  
Tnf Α ◽  
Cord Injury ◽  
Low Level Laser Irradiation

Effect of Every-other-day Fasting on Level of Serum TNF-α in Rats after Acute Spinal Cord Injury

2015 ◽  
Vol 25 (4) ◽  
pp. 14
Author(s):  
Jiancheng LIU ◽  
Wenchun WANG ◽  
Shaojie LUO ◽  
Yanbo LI ◽  
Yunhui ZHAO ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Acute Spinal Cord Injury ◽  
Tnf Α ◽  
Cord Injury

scholarly journals miRNA-221 Regulates Spinal Cord Injury-Induced Inflammatory Response through Targeting TNF-α Expression

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Feng Sun ◽  
Haiwei Zhang ◽  
Tianwen Huang ◽  
Jianhui Shi ◽  
Tianli Wei ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Inflammatory Response ◽  
Mouse Model ◽  
Luciferase Reporter ◽  
Spinal Cord Tissue ◽  
Tnf Α ◽  
Cord Injury ◽  
And Oxidative Stress

Objectives. To investigate the roles of miR-221 in spinal cord injury (SCI) as well as the underlying mechanism. Methods. A mouse model of SCI was generated and used to examine dynamic changes in grip strength of the mouse upper and lower limbs. The expression of miR-221 and tumor necrosis factor-α (TNF-α) was detected by RT-qPCR and Western blot. Levels of inflammation and oxidative stress in microglia cells of the injured mice overexpressing miR-221 were then measured by ELISA. Bioinformatics analysis and dual-luciferase reporter assay were conducted to identify the miR-221 target. Results. We successfully constructed SCI mouse model. The results of qRT-PCR showed that miR-221 was gradually upregulated in the spinal cord tissue of mice in the SCI group with the prolonged injury time. At the same time, the mRNA and protein of TNF-α gradually decreased. We further confirmed through cell experiments that the inflammatory factors TNF-α and IL-6, as well as iNOS and eROS, were upregulated in spinal cord microglia cells of SCI mice, and upregulation of miR-122 can inhibit their expression. Finally, the luciferase reporter experiment confirmed that miR-122 targeted TNF-α. Conclusions. We present evidence that miR-221 promotes functional recovery of the injured spinal cord through targeting TNF-α, while alleviating inflammatory response and oxidative stress.

scholarly journals Ultrashort Wave Combined with Human Umbilical Cord Mesenchymal Stem Cell (HUC-MSC) Transplantation Inhibits NLRP3 Inflammasome and Improves Spinal Cord Injury via MK2/TTP Signalling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Li Na ◽  
Shuai Wang ◽  
Tongtong Liu ◽  
Lixin Zhang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Combination Therapy ◽  
Nlrp3 Inflammasome ◽  
Signalling Pathway ◽  
Regulatory Mechanisms ◽  
Inflammatory Factors ◽  
Expression Levels ◽  
Cord Injury ◽  
Nlrp3 Expression

Objective. To investigate the curative effects of HUC-MSCs combined with USW on spinal cord injury (SCI) and the effects on inflammatory microenvironment and to explore the regulatory mechanisms of MK2/TTP signalling pathway and NLRP3 inflammasome. Methods. The SCI rat model was established using the modified Allen method; rats were administered with USW, HUC-MSCs, and combination therapy of USW and HUC-MSCs; the therapeutic efficacies in each group of rats were monitored and represented in BBB score. SCI levels were observed using HE staining and IF. The microglia polarisation state and released contents of inflammatory factors were detected. IF and Western Blotting were performed on to detect the expression levels of MK2/TTP signalling pathway and NLRP3 inflammasome-related proteins. Furthermore, the regulatory mechanisms of MK2/TTP pathway and NLRP3 were explored by performing on the in vitro study. Results. Combination therapy of USW and HUC-MSCs was found of significant efficacy on improving motor functions of SCI rats, and it was further proved that this combination therapy can reduce spinal cord injury in SCI rats, of which USW plays a more important role. While transplantation of HUC-MSCs can promote microglial cells developing to SCI repair, and M2 microglial cells were taking advantages gradually. The combination therapy can inhibit the expression of MK2; downregulate NLRP3 inflammasome; suppress the expression levels of pro-caspase-1, pro-IL-1β, and pro-IL-18; and simultaneously suppress the release of IL-1β and IL-18, thereby reducing spinal cord neurons apoptosis. It was found that the steady state of microglial polarisation maintained by combined treatment of USW and HUC-MSCs was destroyed with the upregulation of MK2 expression in cells, of which, M1 type microglial cell was dominant and the increased contents of inflammatory factors were detected. However, overexpressed MK2 relieved the inhibition of NLRP3 expression by TTP. Conclusions. Combination therapy of USW and HUC-MSCs can downregulate NLRP3 expression, relieve inflammatory responses, improve immune microenvironment, and rescue spinal cord injury via suppressing phosphorylation level of MK2.

scholarly journals Acute Spinal Cord Injury: Monitoring Lumbar Cerebrospinal Fluid Provides Limited Information about the Injury Site

2020 ◽  
Vol 37 (9) ◽  
pp. 1156-1164 ◽  
Author(s):  
Florence R.A. Hogg ◽  
Mathew J. Gallagher ◽  
Siobhan Kearney ◽  
Argyro Zoumprouli ◽  
Marios C. Papadopoulos ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cerebrospinal Fluid ◽  
Acute Spinal Cord Injury ◽  
Limited Information ◽  
Injury Site ◽  
Cord Injury ◽  
Lumbar Cerebrospinal Fluid

Cerebrospinal Fluid Drainage and Induced Hypertension Improve Spinal Cord Perfusion After Acute Spinal Cord Injury in Pigs

Neurosurgery ◽  
2015 ◽  
Vol 76 (4) ◽  
pp. 461-469 ◽  
Author(s):  
Nikolay L. Martirosyan ◽  
M. Yashar S. Kalani ◽  
William D. Bichard ◽  
Ali A. Baaj ◽  
L. Fernando Gonzalez ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cerebrospinal Fluid ◽  
Acute Spinal Cord Injury ◽  
Cerebrospinal Fluid Drainage ◽  
Cord Injury ◽  
Induced Hypertension
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