title: Regulation of mice liver regeneration by early growth response-1 through the GGPPS/RAS/MAPK pathway.
abstract: OBJECTIVE
  Liver regeneration (LR) consists of a series of complicated processes in which several transcription factors play important roles. Among them, the early growth response 1 gene (EGR-1) is rapidly induced in response to liver resection. Previous studies have shown that EGR-1-/- mice exhibit delayed hepatocellular mitotic progression after partial hepatectomy (PH). The mechanism underlying the EGR-1 regulated LR is still unknown. Our aim is to elucidate the underlying mechanism.
  
  
  METHODS
  Mice infected with adenoviral vectors expressing GFP, EGR-1 or dominant negative EGR-1 (dnEGR-1) were subjected to 2/3 PH. The serum starvation recovery cell model was chosen to mimic the regeneration process for the in vitro studies. Cell proliferation and signaling pathways downstream of geranylgeranyl diphosphate synthase (GGPPS) were examined in the regenerating liver and serum starvation recovery cell model.
  
  
  RESULTS
  Loss of function of EGR-1 significantly inhibited liver recovery and the expression of cyclin D1, cyclin E, and proliferating cell nuclear antigen (PCNA). The expression of GGPPS and the activity of the downstream RAS/MAPK pathway were inhibited in dnEGR-1-infected liver, which was consistent with the serum-induced cell model. In addition, loss of function of EGR-1 aggravated liver damage with increased serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels.
  
  
  CONCLUSIONS
  EGR-1-induced GGPPS plays a vital role in the LR after PH through the RAS/MAPK signaling.
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University and Model Animal Research Center, National Resource Center for Mutant Mice, Nanjing, 210093, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Lai
authors.affiliation: Biochemical and Environmental Engineering School of Xiaozhuang Collage, Nanjing 211171, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University and Model Animal Research Center, National Resource Center for Mutant Mice, Nanjing, 210093, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University and Model Animal Research Center, National Resource Center for Mutant Mice, Nanjing, 210093, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Shen
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University and Model Animal Research Center, National Resource Center for Mutant Mice, Nanjing, 210093, China; Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210093, China.
authors.forename: Weibo
authors.initials: W
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Nanjing Normal University, Nanjing 210097, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210093, China.
authors.forename: Decai
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory for Molecular and Medical Biotechnology, Nanjing Normal University, Nanjing 210097, China.
authors.forename: Feiyan
authors.initials: F
authors.lastname: Pan
authors.affiliation: MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center and the School of Medicine, Nanjing University, National Resource Center for Mutant Mice, Nanjing 210093, China.
authors.forename: Minsheng
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University and Model Animal Research Center, National Resource Center for Mutant Mice, Nanjing, 210093, China. Electronic address: licj@nju.edu.cn.
authors.forename: Chaojun
authors.initials: C
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University and Model Animal Research Center, National Resource Center 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; D002460:Cell Line; D004261:DNA Replication; D051766:Early Growth Response Protein 1 / Q000502:physiology*; D051231:Farnesyltranstransferase / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D008115:Liver Regeneration; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D018631:ras Proteins / Q000378:metabolism
chemical_list: D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; C495428:Ggps1 protein, mouse; D009097:Multienzyme Complexes; D051231:Farnesyltranstransferase; D018631:ras Proteins
keywords: EGR-1; GGPPS; Liver regeneration; MAPK; Serum starvation recovery