• Open Access

Hepatic miR-29ab1 expression modulates chronic hepatic injury

Authors

  • Takayuki Kogure,

    1. College of Medicine, Ohio State University, Columbus, OH, USA
    2. Department of Transplantation, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
    Search for more papers by this author
    • These authors contributed equally to the work.
  • Stefan Costinean,

    1. College of Medicine, Ohio State University, Columbus, OH, USA
    Search for more papers by this author
    • These authors contributed equally to the work.
  • Irene Yan,

    1. Department of Transplantation, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
    Search for more papers by this author
  • Chiara Braconi,

    1. College of Medicine, Ohio State University, Columbus, OH, USA
    Search for more papers by this author
  • Carlo Croce,

    1. College of Medicine, Ohio State University, Columbus, OH, USA
    Search for more papers by this author
  • Tushar Patel

    Corresponding author
    1. College of Medicine, Ohio State University, Columbus, OH, USA
    2. Department of Transplantation, Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
    • Correspondence to: Tushar PATEL, MBChB, AGAF, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA.

      Tel.: +1 904 956 3257

      Fax: +1 904 956 3359

      E-mail:patel.tushar@mayo.edu

    Search for more papers by this author

Abstract

MicroRNAs (miRNAs) are small, regulatory non-coding RNAs that have potent effects on gene expression. Several miRNA are deregulated in cellular processes involved in human liver diseases and regulation of cellular processes. Recent studies have identified the involvement of miR-29 in hepatic fibrosis and carcinogenesis. Although several targets of miR-29 have been identified, there is limited information regarding the cell-type specific roles of miR-29 in the liver, and we sought to evaluate the role of this miRNA in hepatic pathobiology. We report the generation of a tissue–specific knockout mouse to evaluate the role of miR-29 in hepatic fibrosis and carcinogenesis in response to injury. We hypothesized that miR-29 contributes to the hepatocyte driven response to chronic cellular injury that results in fibrosis. In support of this hypothesis, fibrosis and mortality were enhanced in miR29 knockout mice in response to carbon tetrachloride. Genome-wide gene expression analysis identified an over-representation of genes associated with fibrosis. The oncofetal RNA H19 was modulated in a miR-29 dependent manner following exposure to carbon tetrachloride in vivo. The impact of a hepatocyte specific miR-29 knockout on survival following chronic hepatic injury in vivo implicates this miRNA as a potential target for intervention. These results provide evidence of the involvement of miR-29 in chronic hepatic injury, and suggest a role for deregulated hepatocyte expression of miR-29 in the response to hepatic injury, fibrosis and carcinogenesis.

Ancillary