title: GGPPS deficiency aggravates CCl4-induced liver injury by inducing hepatocyte apoptosis.
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.
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China; Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China.
authors.forename: Wei-Bo
authors.initials: WB
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China; MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Centre and the School of Medicine, Nanjing University, National Resource Centre for Mutant Mice, Nanjing 210093, China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Lai
authors.affiliation: Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China.
authors.forename: De-Cai
authors.initials: DC
authors.lastname: Yu
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China; MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Centre and the School of Medicine, Nanjing University, National Resource Centre for Mutant Mice, Nanjing 210093, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China; MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Centre and the School of Medicine, Nanjing University, National Resource Centre for Mutant Mice, Nanjing 210093, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China; MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Centre and the School of Medicine, Nanjing University, National Resource Centre for Mutant Mice, Nanjing 210093, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Zhao
authors.affiliation: Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China. Electronic address: yitao_ding1@163.com.
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Ding
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China; MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Centre and the School of Medicine, Nanjing University, National Resource Centre for Mutant Mice, Nanjing 210093, China. Electronic address: licj@nju.edu.cn.
authors.forename: Chao-Jun
authors.initials: CJ
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China; MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Centre and the School of Medicine, Nanjing University, National Resource Centre for Mutant Mice, Nanjing 210093, China. Electronic address: xuebin@nju.edu.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Xue
mesh_terms: D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051231:Farnesyltranstransferase / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D022781:Hepatocytes / Q000201:enzymology* / Q000473:pathology; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011106:Polyisoprenyl Phosphates / Q000096:biosynthesis; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D011106:Polyisoprenyl Phosphates; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D051231:Farnesyltranstransferase; C002963:geranylgeranyl pyrophosphate
keywords: Geranylgeranyl diphosphate synthase; Hepatocyte apoptosis; Liver fibrosis; Liver injury