Hepatic miR-29ab1 expression modulates chronic hepatic injury

Takayuki Kogure, Stefan Costinean, Irene Yan, Chiara Braconi, Carlo Croce, Tushar C Patel

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2647-2654
Number of pages8
JournalJournal of Cellular and Molecular Medicine
Volume16
Issue number11
DOIs
StatePublished - Nov 2012

Fingerprint

Fibrosis
MicroRNAs
Liver
Wounds and Injuries
Hepatocytes
Carcinogenesis
Carbon Tetrachloride
Knockout Mice
Gene Expression
Small Untranslated RNA
Liver Diseases
Genome
Survival
Mortality
Genes

Keywords

  • Fibrosis
  • Liver cancer
  • Transgenic

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Cite this

Hepatic miR-29ab1 expression modulates chronic hepatic injury. / Kogure, Takayuki; Costinean, Stefan; Yan, Irene; Braconi, Chiara; Croce, Carlo; Patel, Tushar C.

In: Journal of Cellular and Molecular Medicine, Vol. 16, No. 11, 11.2012, p. 2647-2654.

Research output: Contribution to journalArticle

Kogure, Takayuki ; Costinean, Stefan ; Yan, Irene ; Braconi, Chiara ; Croce, Carlo ; Patel, Tushar C. / Hepatic miR-29ab1 expression modulates chronic hepatic injury. In: Journal of Cellular and Molecular Medicine. 2012 ; Vol. 16, No. 11. pp. 2647-2654.
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