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首页> 外文期刊>Toxicology and Applied Pharmacology >HMGA2, a driver of inflammation, is associated with hypermethylation in acute liver injury
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HMGA2, a driver of inflammation, is associated with hypermethylation in acute liver injury

机译：HMGA2，炎症的驾驶员，与急性肝损伤中的高甲基化有关

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摘要

Acute liver injury (ALI) is characteristic of abrupt hepatic dysfunction and inflammatory response. Activaion of Kupffer cells (KCs) plays a central role in the pathogenesis of ALI. Since the High Mobility Group A protein2 (HMGA2) occurs as a driver at critical stage of hepatocellular carcinoma, herein, we investigated the role of HMGA2 in macrophage activation during ALI. Our study found that the expression of HMGA2 decreased dramatically both in KCs isolated from the liver in mice with ALI and in LPS-induced RAW264.7 cell lines. Moreover, loss and gain-of-function studies suggested that HMGA2 could enhance the expression of pro-inflammatory cytokines including TNF-alpha, IL-6 and IL-1 beta. These results indicated that HMGA2 may play an essential role in macrophage activation during ALI. Additionally, our results showed the expression of HMGA2 was up-regulated when LPS-induced RAW264.7 cells were treated with 5-aza-2-deoxycytidine. Furthermore, silencing of DNMT1, DNMT3a, DNMT3b could respectively prevent the down-expression of HMGA2 in LPS-induced RAW264.7 cells. In conclusion, HMGA2 promotes the release of pro-inflammatory cytokines through NF-kappa B pathway, and the dysregulation of HMGA2 may involve with hypermethylation. (C) 2017 Published by Elsevier Inc.
机译：急性肝损伤（ALI）以突发性肝功能障碍和炎症反应为特征。库普弗细胞（KCs）的激活在ALI的发病机制中起着核心作用。由于高迁移率族A蛋白2（HMGA2）在肝细胞癌的关键阶段是一个驱动因素，因此我们在此研究了HMGA2在ALI期间巨噬细胞活化中的作用。我们的研究发现，在ALI小鼠肝脏分离的KC和LPS诱导的RAW264中，HMGA2的表达显著降低。7个细胞系。此外，功能丧失和功能增强研究表明，HMGA2可增强促炎细胞因子的表达，包括TNF-α、IL-6和IL-1β。这些结果表明HMGA2可能在ALI期间巨噬细胞活化中发挥重要作用。此外，我们的结果显示，当LPS诱导RAW264时，HMGA2的表达上调。7个细胞用5-氮杂-2-脱氧胞苷处理。此外，沉默DNMT1、DNMT3a和DNMT3b可分别阻止LPS诱导的RAW264中HMGA2的表达下调。7个单元格。总之，HMGA2通过NF-κB途径促进促炎细胞因子的释放，HMGA2的失调可能与高甲基化有关。（C） 2017年由爱思唯尔公司出版。

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  • 来源
    《Toxicology and Applied Pharmacology》 |2017年第2017期|共12页
  • 作者

    Huang Huimin; Li Haidi; Chen Xin; Yang Yang; Li Xiaofeng; Li Wanxia; Huang Cheng; Meng Xiaoming; Zhang Lei; Li Jun;

  • 作者单位

    Anhui Med Univ Key Lab Major Autoimmune Dis Anhui Inst Innovat Drugs Sch Pharm Hefei Anhui;

    Anhui Med Univ Key Lab Major Autoimmune Dis Anhui Inst Innovat Drugs Sch Pharm Hefei Anhui;

    Anhui Med Univ Key Lab Major Autoimmune Dis Anhui Inst Innovat Drugs Sch Pharm Hefei Anhui;

    Anhui Med Univ Key Lab Major Autoimmune Dis Anhui Inst Innovat Drugs Sch Pharm Hefei Anhui;

    Anhui Med Univ Key Lab Major Autoimmune Dis Anhui Inst Innovat Drugs Sch Pharm Hefei Anhui;

    Anhui Med Univ Key Lab Major Autoimmune Dis Anhui Inst Innovat Drugs Sch Pharm Hefei Anhui;

    Anhui Med Univ Key Lab Major Autoimmune Dis Anhui Inst Innovat Drugs Sch Pharm Hefei Anhui;

    Anhui Med Univ Key Lab Major Autoimmune Dis Anhui Inst Innovat Drugs Sch Pharm Hefei Anhui;

    Anhui Med Univ Key Lab Major Autoimmune Dis Anhui Inst Innovat Drugs Sch Pharm Hefei Anhui;

    Anhui Med Univ Key Lab Major Autoimmune Dis Anhui Inst Innovat Drugs Sch Pharm Hefei Anhui;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 毒物学（毒理学）;
  • 关键词

    HMGA2; Acute liver injury (ALI); Kupffer cells (KCs); RAW264.7 cells; Hypermethylation;

    机译：HMGA2;急性肝损伤（ALI）;Kupffer细胞（KCS）;RAW264.7细胞;高甲基化;

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