1. GGPPSdeficiency aggravates CCl4-induced liver injury by inducing hepatocyte apoptosis
- Author
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Bin Xue, Shan-Shan Lai, Dan-Dan Zhao, Chao-Jun Li, Yitao Ding, Wei-Bo Chen, Jia Liu, Shan Jiang, and Decai Yu
- Subjects
Liver Cirrhosis ,MAPK/ERK pathway ,Liver fibrosis ,Biophysics ,Inflammation ,Liver injury ,Biochemistry ,Transforming Growth Factor beta1 ,Hepatocyte apoptosis ,Mice ,Polyisoprenyl Phosphates ,Structural Biology ,Fibrosis ,Genetics ,medicine ,Animals ,Farnesyltranstransferase ,Molecular Biology ,Glyceraldehyde 3-phosphate dehydrogenase ,Mice, Knockout ,biology ,Carbon Tetrachloride Poisoning ,Cell Biology ,medicine.disease ,Geranylgeranyl diphosphate synthase ,CTGF ,Liver ,HMG-CoA reductase ,Hepatocytes ,biology.protein ,Cancer research ,Hepatic stellate cell ,medicine.symptom ,Gene Deletion - Abstract
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.
- Published
- 2015
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