首页> 外文期刊>Cell biology international. >MicroRNA‐34a‐5p inhibits liver fibrosis by regulating TGF‐β1/Smad3 pathway in hepatic stellate cells
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MicroRNA‐34a‐5p inhibits liver fibrosis by regulating TGF‐β1/Smad3 pathway in hepatic stellate cells

机译:MicroRNA-34A-5P通过调节肝星状细胞中的TGF-β1/ SMAD3途径来抑制肝纤维化

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摘要

Abstract Liver fibrosis is a major cause of morbidity and mortality worldwide, and the outcome of various chronic liver diseases. Recent studies suggest that aberrant expression of miR‐34 is involved in the progression of various liver diseases including hepatocellular carcinoma (HCC). However, it is still poorly understood whether miR‐34 mediates the pathogenesis of liver fibrosis. Here, we found that the expression of microRNA‐34a‐5p (miR‐34a‐5p) was significantly decreased in patients with hepatitis B virus (HBV)‐activated liver fibrosis and HCC, as well as in CC14 (Carbon tetrachloride Tetrachloromethane) induced liver fibrosis model mice. The TGF‐β1/Smad3 (Transforming growth factor‐β1/Smad3) pathway were significantly augmented in CC14 induced mice compared with normal control, whereas inhibitor of TGF‐β1 (SB431542) significantly attenuated liver fibrosis and TGF‐β1/Smad3 activation. Administration of the miR‐34a‐5p mimic de‐activated TGF‐β1/Smad3 pathway in human hepatic stellate cells (HSC), LX‐2. Moreover, the target gene for miR‐34a‐5p, Smad4, was predicted and verified in LX‐2 cells. Taken together, these data demonstrated that overexpression of miR‐34 in HSCs ameliorated the development and progression of liver fibrosis by targeting Smad4 and regulating TGF‐β1/Smad3 pathway. Strategies targeting miR‐34a‐5p may be of benefit in the treatment of liver fibrosis.
机译:摘要肝纤维化是全世界发病率和死亡率的主要原因,以及各种慢性肝病的结果。最近的研究表明miR-34的异常表达涉及各种肝脏疾病的进展,包括肝细胞癌(HCC)。然而,米尔-34是否介导肝纤维化的发病机制,仍然是较差的。在这里,我们发现MicroRNA-34A-5P(MIR-34A-5P)的表达在乙型肝炎病毒(HBV) - 活化的肝纤维化和HCC患者中显着降低,以及诱导的CC14(四氯化碳四氯甲烷)肝纤维化模型小鼠。 CC14诱导小鼠的TGF-β1/ smad3(转化生长因子-β1/ smad3)途径显着增强了与正常对照相比,而TGF-β1(SB431542)的抑制剂显着减弱肝纤维化和TGF-β1/ SMAD3活化。在人肝星状细胞(HSC),LX-2中施用miR-34a-5p模拟的去活化TGF-β1/ smad3途径。此外,预测MIR-34A-5P,SMAD4的靶基因并在LX-2细胞中验证。总之,这些数据表明,通过靶向SMAD4和调节TGF-β1/ SMAD3途径,对HSC中的miR-34的过度表达改善了肝纤维化的开发和进展。靶向miR-34a-5p的策略可能是有益的肝纤维化。

著录项

  • 来源
    《Cell biology international.》 |2018年第10期|共7页
  • 作者单位

    Department of Infectious DiseasesYiWu Central HospitaNo 699 Jiangdong Road Yiwu Zhejiang 322000;

    Department of Infectious DiseasesYiWu Central HospitaNo 699 Jiangdong Road Yiwu Zhejiang 322000;

    Department of Infectious DiseasesYiWu Central HospitaNo 699 Jiangdong Road Yiwu Zhejiang 322000;

    Department of Infectious DiseasesYiWu Central HospitaNo 699 Jiangdong Road Yiwu Zhejiang 322000;

    Department of Infectious DiseasesYiWu Central HospitaNo 699 Jiangdong Road Yiwu Zhejiang 322000;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    liver fibrosis; miR‐34a‐5p; TGF‐β1/Smad3 pathway; Smad4;

    机译:肝纤维化;miR-34a-5p;tgf-β1/ smad3途径;smad4;

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