These authors contributed equally to the work.
Hepatic miR-29ab1 expression modulates chronic hepatic injury
Article first published online: 29 OCT 2012
© 2012 The Authors Journal of Cellular and Molecular Medicine © 2012 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
Journal of Cellular and Molecular Medicine
Volume 16, Issue 11, pages 2647–2654, November 2012
How to Cite
Kogure, T., Costinean, S., Yan, I., Braconi, C., Croce, C. and Patel, T. (2012), Hepatic miR-29ab1 expression modulates chronic hepatic injury. Journal of Cellular and Molecular Medicine, 16: 2647–2654. doi: 10.1111/j.1582-4934.2012.01578.x
- Issue published online: 29 OCT 2012
- Article first published online: 29 OCT 2012
- Accepted manuscript online: 31 MAR 2012 10:13AM EST
- Manuscript Accepted: 27 MAR 2012
- Manuscript Received: 21 NOV 2011
- National Institutes of Health. Grant Number: DK069370
- liver cancer;
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.