EZH2 Mediates miR-146a-5p/HIF-1α to Alleviate Inflammation and Glycolysis after Acute Spinal Cord Injury.
EZH2 Mediates miR-146a-5p/HIF-1α to Alleviate Inflammation and Glycolysis after Acute Spinal Cord Injury.
复制标题
EZH2 介导 miR-146a-5p/HIF-1 α 以减轻急性脊髓损伤后的炎症和糖酵解
DOI：
10.1155/2021/5591582
复制
发表时间：
2021
影响因子：
4.6
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Ni S;Yang B;Xia L;Zhang H
急性脊髓损伤（acute spinal cord injury，ASCI）是一种严重的中枢神经系统创伤性疾病，其发病机制尚不清楚。本研究旨在探讨EZH 2和miR-146 a-5 p/HIF-1α在ASCI后炎症和糖酵解中的作用，为ASCI损伤的临床治疗和预后提供参考和依据。采用脂多糖（LPS）诱导小胶质细胞炎症反应，建立ASCI动物模型。qRT-PCR检测EZH 2、HIF-1α、miR-146 a-5 p、IL-6、TNF-α、IL-17、PKM 2、GLUT 1和HK 2在细胞和组织中的相对表达水平。Western blot检测EZH 2、HIF-1α、H3 K27 me 3、IL-6、TNF-α、IL-17、PKM 2、GLUT 1和HK 2的表达水平。ChIP验证了H3 K27 me 3在miR-146 a-5 p启动子区的富集。生物信息学预测了HIF-1α与miR-146 a-5 p的结合位点，双荧光素酶报告基因分析验证了HIF-1α与miR-146 a-5 p的结合。ELISA法检测大鼠脑脊液中炎性因子IL-6、TNF-α和IL-17的水平。采用GC-TOFMS检测大鼠脑脊液中糖酵解代谢产物的变化。EZH 2可介导小胶质细胞的炎症和糖酵解。EZH 2通过HIF-1α调节炎症和糖酵解。EZH 2通过介导miR-146 a-5 p间接调控HIF-1α的表达。EZH 2介导miR-146 a-5 p/HIF-1α减轻ASCI大鼠的炎症和糖酵解本研究结果表明，EZH 2可以介导miR-146 a-5 p/HIF-1α减轻ASCI后的炎症和糖酵解。因此，EZH 2/miR-146 a-5 p/HIF-1α可能成为治疗ASCI的新靶点。
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.
登录
查看更多内容
EZH2 通过 EAF2-HIF1 α 信号的表观遗传抑制促进胶质母细胞瘤中的代谢重编程
影响因子：
--
作者：
Pang B;Zheng XR;Tian JX;Gao TH;Gu GY;Zhang R;Fu YB;Pang Q;Li XG;Liu Q
通讯作者：
Liu Q
影响因子：
4.3
作者：
Carpenter KL;Jalloh I;Hutchinson PJ
通讯作者：
Hutchinson PJ
DOI：
10.1016/j.biocel.2020.105826
发表时间：
2020-10-01
影响因子：
4
作者：
Li, Shiyuan;Zeng, Ming;Li, Jiaying
通讯作者：
Li, Jiaying
影响因子：
4.2
作者：
Lv, Youyou;Zhang, Bo;Zhang, Chuanhan
通讯作者：
Zhang, Chuanhan
影响因子：
10.8
作者：
Lambert, Caroline M.;Roy, Melanie;Bonnet, Sebastien
通讯作者：
Bonnet, Sebastien