Hepatic mi R ‐29ab1 expression modulates chronic hepatic injury

Micro RNA s (mi RNA s) are small, regulatory non‐coding RNA s that have potent effects on gene expression. Several mi RNA are deregulated in cellular processes involved in human liver diseases and regulation of cellular processes. Recent studies have identified the involvement of mi R ‐29 in hepatic fibrosis and carcinogenesis. Although several targets of mi R ‐29 have been identified, there is limited information regarding the cell‐type specific roles of mi R ‐29 in the liver, and we sought to evaluate the role of this mi RNA in hepatic pathobiology. We report the generation of a tissue–specific knockout mouse to evaluate the role of mi R ‐29 in hepatic fibrosis and carcinogenesis in response to injury. We hypothesized that mi R ‐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 mi R 29 knockout mice in response to carbon tetrachloride. Genome‐wide gene expression analysis identified an over‐representation of genes associated with fibrosis. The oncofetal RNA H 19 was modulated in a mi R ‐29 dependent manner following exposure to carbon tetrachloride in vivo . The impact of a hepatocyte specific mi R ‐29 knockout on survival following chronic hepatic injury in vivo implicates this mi RNA as a potential target for intervention. These results provide evidence of the involvement of mi R ‐29 in chronic hepatic injury, and suggest a role for deregulated hepatocyte expression of mi R ‐29 in the response to hepatic injury, fibrosis and carcinogenesis.