The functional role of microRNAs in alcoholic liver injury

Authors

  • Kelly McDaniel,

    1. Research, Central Texas Veterans Health Care System, Temple, TX, USA
    2. Department of Medicine, Scott & White Digestive Disease Research Center, Texas A&M University Health Science Center and Scott & White Healthcare, Temple, TX, USA
    3. Academic Operations, Scott & White Hospital, Temple, TX, USA
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    • These authors contributed equally to this article.
  • Leonardo Herrera,

    1. Texas Bioscience Institute, Temple, TX, USA
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    • These authors contributed equally to this article.
  • Tianhao Zhou,

    1. Department of Medicine, Scott & White Digestive Disease Research Center, Texas A&M University Health Science Center and Scott & White Healthcare, Temple, TX, USA
    2. Academic Operations, Scott & White Hospital, Temple, TX, USA
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  • Heather Francis,

    1. Research, Central Texas Veterans Health Care System, Temple, TX, USA
    2. Department of Medicine, Scott & White Digestive Disease Research Center, Texas A&M University Health Science Center and Scott & White Healthcare, Temple, TX, USA
    3. Academic Operations, Scott & White Hospital, Temple, TX, USA
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  • Yuyan Han,

    1. Research, Central Texas Veterans Health Care System, Temple, TX, USA
    2. Department of Medicine, Scott & White Digestive Disease Research Center, Texas A&M University Health Science Center and Scott & White Healthcare, Temple, TX, USA
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  • Phillip Levine,

    1. Research, Central Texas Veterans Health Care System, Temple, TX, USA
    2. Department of Medicine, Scott & White Digestive Disease Research Center, Texas A&M University Health Science Center and Scott & White Healthcare, Temple, TX, USA
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  • Emily Lin,

    1. Texas Bioscience Institute, Temple, TX, USA
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  • Shannon Glaser,

    1. Research, Central Texas Veterans Health Care System, Temple, TX, USA
    2. Department of Medicine, Scott & White Digestive Disease Research Center, Texas A&M University Health Science Center and Scott & White Healthcare, Temple, TX, USA
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  • Gianfranco Alpini,

    Corresponding author
    1. Research, Central Texas Veterans Health Care System, Temple, TX, USA
    2. Department of Medicine, Scott & White Digestive Disease Research Center, Texas A&M University Health Science Center and Scott & White Healthcare, Temple, TX, USA
    • Address for correspondence: Fanyin MENG, Ph.D. or Gianfranco ALPINI, Ph.D., Digestive Disease Research Center, Scott & White Healthcare, Texas A&M Health Science Center College of Medicine, 1901 S 1st Street, Building 205, Room 1R60, Temple, TX 76504, USA.

      Tel.: 254-743-0383 or 254-743-0274

      Fax: 254-743-0555 or 254-743-0378

      E-mail: fmeng@tamu.edu or galpini@tamu.edu

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  • Fanyin Meng

    Corresponding author
    1. Research, Central Texas Veterans Health Care System, Temple, TX, USA
    2. Department of Medicine, Scott & White Digestive Disease Research Center, Texas A&M University Health Science Center and Scott & White Healthcare, Temple, TX, USA
    3. Academic Operations, Scott & White Hospital, Temple, TX, USA
    • Address for correspondence: Fanyin MENG, Ph.D. or Gianfranco ALPINI, Ph.D., Digestive Disease Research Center, Scott & White Healthcare, Texas A&M Health Science Center College of Medicine, 1901 S 1st Street, Building 205, Room 1R60, Temple, TX 76504, USA.

      Tel.: 254-743-0383 or 254-743-0274

      Fax: 254-743-0555 or 254-743-0378

      E-mail: fmeng@tamu.edu or galpini@tamu.edu

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Abstract

The function of microRNAs (miRNAs) during alcoholic liver disease (ALD) has recently become of great interest in biological research. Studies have shown that ALD associated miRNAs play a crucial role in the regulation of liver-inflammatory agents such as tumour necrosis factor-alpha (TNF-α), one of the key inflammatory agents responsible for liver fibrosis (liver scarring) and the critical contributor of alcoholic liver disease. Lipopolysaccharide (LPS), a component of the cell wall of gram-negative bacteria, is responsible for TNF-α release by Kupffer cells. miRNAs are the critical mediators of LPS signalling in Kupffer cells, hepatocytes and hepatic stellate cells. Certain miRNAs, in particular miR-155 and miR-21, show a positive correlation in up-regulation of LPS signalling when they are exposed to ethanol. ALD is related to enhanced gut permeability that allows the levels of LPS to increase, leads to increased secretion of TNF-α by the Kupffer cells and subsequently promotes alcoholic liver injury through specific miRNAs. Meanwhile, two of the most frequently dysregulated miRNAs in steatohepatitis, miR-122 and miR-34a are the critical mediators in ethanol/LPS activated survival signalling during ALD. In this review, we summarize recent findings regarding the experimental and clinical aspects of functions of specific microRNAs, focusing mainly on inflammation and cell survival after ethanol/LPS treatment, and advances on the role of circulating miRNAs in human alcoholic disorders.

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