geranylgeranyl-pyrophosphate and Liver-Cirrhosis

GGPPS catalyses the expression of GGPP, a key protein in the mevalonate metabolic pathway. HMG-CoA reductase inhibitor statins can induce liver injury by inhibiting GGPP. However, the function of GGPPS in liver injury has not yet been revealed. In this study, we found that GGPPS increased in liver injury and that GGPPS deletion augmented liver injury and fibrosis. GGPPS inhibition induced hepatocyte apoptosis, inflammation and TGF-β1 secretion, which activated hepatic stellate cells. Our findings imply that GGPPS deletion induces hepatocyte apoptosis, which makes the liver vulnerable to hepatotoxicity.

Topics: Animals; Carbon Tetrachloride Poisoning; Farnesyltranstransferase; Gene Deletion; Hepatocytes; Liver; Liver Cirrhosis; Mice; Mice, Knockout; Polyisoprenyl Phosphates; Transforming Growth Factor beta1