GGPPS deficiency aggravates CCl4‐induced liver injury by inducing hepatocyte apoptosis. Issue 10 (24th March 2015)

• Record Type: Journal Article
• Authors: Chen, Wei-Bo; Lai, Shan-Shan; Yu, De-Cai; Liu, Jia; Jiang, Shan; Zhao, Dan-Dan; Ding, Yi-Tao; Li, Chao-Jun; Xue, Bin
• Is Part Of: FEBS letters. Volume 589:Issue 10(2015)
• Page Start: 1119
• Page End: 1126
• Publication Date: 2015-03-24
• Subjects: GGPPS -- geranylgeranyl diphosphate synthase -- GGPP -- geranylgeranyl pyrophosphate -- HMG-CoA -- 3-hydroxy-3-methylglutarylcoenzyme A -- CCl4 -- carbon tetrachloride -- ECM -- extracellular matrix -- COL1A1 -- type I collagen -- HCV -- hepatitis C virus -- NASH -- non-alcoholic steatohepatitis -- HSC -- hepatic stellate cells -- pIpC -- polyriboinosinic-polyribocytidylic -- PARP -- poly ADP-ribose polymerase -- GAPDH -- glyceraldehyde-3-phosphate dehydrogenase -- FBS -- foetal bovine serum -- shRNA -- short hairpin RNA -- α-SMA -- α-smooth muscle actin -- WT -- wild type -- CTGF -- connective tissue growth factor -- TGF-β1 -- transforming growth factor-beta 1 -- PDGF -- platelet-derived growth factor -- FPP -- farnesyl pyrophosphate -- PCNA -- proliferating cell nuclear antigen -- TNF-α -- tumour necrosis factor-alpha -- MAPK -- mitogen-activated protein kinase -- HCC -- hepatocellular carcinoma -- Geranylgeranyl diphosphate synthase -- Liver injury -- Liver fibrosis -- Hepatocyte apoptosis; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2015.03.015
• Languages: English
• ISSNs: 0014-5793

Abstract

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. Abstract : GGPPS increases in liver injury. GGPPS deletion augments CCl4 ‐induced liver injury and fibrosis in mice. GGPPS expression interference in hepatocytes induces apoptosis. Deletion of GGPPS in hepatocytes activates hepatic stellate cells by promoting inflammation and TGF‐β1 secretion.