Journal
FEBS LETTERS
Volume 589, Issue 10, Pages 1119-1126Publisher
WILEY
DOI: 10.1016/j.febslet.2015.03.015
Keywords
Geranylgeranyl diphosphate synthase; Liver injury; Liver fibrosis; Hepatocyte apoptosis
Funding
- Chinese National Science Foundation [30700794, 31171306, 31371373]
- Nature Science Foundation of Jiangsu Province [BK2011568]
- National Basic Research Program of China (973 program) [2012CB524900]
- Medical Science and Technology Development Foundation, Nanjing Department of Health [ZKX12030]
- Jiangsu Province Innovation for Ph.D. Candidates [KYLX_0058]
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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-beta 1 secretion, which activated hepatic stellate cells. Our findings imply that GGPPS deletion induces hepatocyte apoptosis, which makes the liver vulnerable to hepatotoxicity. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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