title: Pre-stimulated Mice with Carbon Tetrachloride Accelerate Early Liver Regeneration After Partial Hepatectomy.
abstract: OBJECTIVE
  The liver has a high capacity of its regeneration. Most hepatic cells are quiescent unless otherwise stimulated such as their injury or ablation. A previous study suggest that pre-activated hepatic cells have a positive effect on their regeneration. In this study, we examined whether the pre-activated hepatic cells for regeneration accelerate the subsequent liver regeneration.
  
  
  METHODS
  We administered a single injection of carbon tetrachloride (CCl4) to mice 7 days before partial hepatectomy (PHx). Liver weight/body weight ratio and several parameters for cell proliferation such as mitotic index and the number of Ki67 positive cells in the liver were examined after PHx as indexes of liver regeneration.
  
  
  RESULTS
  Compared to control mice, those pre-stimulated with CCl4 showed earlier liver regeneration 48 h after PHx. Regardless of their accelerated regeneration, pre-stimulated mice showed less cell proliferation than did control mice during liver regeneration. Hepatic fibrosis was not observed in both control and CCl4-pretreated mice after PHx. Mice pre-treated with CCl4 showed the higher matrix metalloproteinase 9 (MMP9) expression than those pre-treated with olive oil. When matrix metalloproteinase 9 (MMP9) activity was inhibited, the pre-stimulated mice did not demonstrate accelerated liver regeneration and they returned to the original state for cell proliferations after PHx.
  
  
  CONCLUSIONS
  Pre-activated liver by CCl4 promoted its subsequent regeneration after PHx. This was not a cause of fibrosis and partly dependent on MMP9 pre-activity rather than cell proliferation in liver. Our findings would not only provide a novel strategy for liver regeneration without cell proliferation as much as possible and also propose a new method for liver transplantation.
authors: Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan, ariokay@gifu-u.ac.jp.
authors: Yuko
authors: Y
authors: Arioka
authors: Hiroyasu
authors: H
authors: Ito
authors: Tatsuya
authors: T
authors: Ando
authors: Hideyuki
authors: H
authors: Ogiso
authors: Akihiro
authors: A
authors: Hirata
authors: Akira
authors: A
authors: Hara
authors: Mitsuru
authors: M
authors: Seishima
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D049109:Cell Proliferation; D006498:Hepatectomy; D008115:Liver Regeneration / Q000187:drug effects*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D012313:RNA / Q000302:isolation & purification; D013997:Time Factors; D014280:Triglycerides / Q000032:analysis
chemical_list: D014280:Triglycerides; D012313:RNA; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase; D020780:Matrix Metalloproteinase 9
references: Mol Cell Biol. 2003 Sep;23(17):6159-73
references: 12917338
references: J Gastroenterol Hepatol. 1998 Sep;13(S1):S100-S105
references: 28976695
references: Nature. 2014 Jan 2;505(7481):97-102
references: 24256728
references: Toxicol Pathol. 2005;33(1):41-51
references: 15805055
references: Am J Pathol. 2007 Feb;170(2):567-77
references: 17255325
references: Biomaterials. 2004 Apr;25(9):1601-11
references: 14697862
references: J Hepatol. 2014 May;60(5):1032-9
references: 24412604
references: Indian J Biochem Biophys. 2003 Oct;40(5):324-9
references: 22900326
references: Adv Biochem Eng Biotechnol. 2005;93:101-34
references: 15791946
references: Curr Biol. 2012 Jul 10;22(13):1166-75
references: 22658593
references: J Surg Res. 2013 Jan;179(1):66-71
references: 23110972
references: J Surg Res. 2013 Dec;185(2):545-6
references: 23312814
references: Blood. 2010 Jul 29;116(4):544-53
references: 20442369
references: J Hepatol. 2012 Sep;57(3):692-4
references: 22613006
references: Hepatology. 2003 Nov;38(5):1116-24
references: 14578850
references: Cytometry. 1996 Sep 1;25(1):1-13
references: 8875049
references: J Lipid Res. 1970 Nov;11(6):536-43
references: 5504519
references: J Cell Physiol. 2007 Nov;213(2):286-300
references: 17559071
references: Science. 2014 Jan 24;343(6169):416-9
references: 24458641
references: Hepatology. 2006 Sep;44(3):540-9
references: 16941692
references: Histochem Cell Biol. 1999 Oct;112(4):277-82
references: 10550612
references: Dig Dis Sci. 2009 Sep;54(9):1918-25
references: 19104935
references: Am J Physiol Gastrointest Liver Physiol. 2009 Sep;297(3):G419-33
references: 19497955
references: J Surg Res. 2013 Mar;180(1):156-61
references: 23157925
references: Hepatology. 2012 Oct;56(4):1489-98
references: 22707117
references: PLoS One. 2013;8(3):e59836
references: 23527275
references: Hepatology. 2012 Jan;55(1):244-55
references: 21898476
references: Liver Int. 2010 Nov;30(10):1414-26
references: 20633100
references: Scand J Gastroenterol. 2014 Jan;49(1):99-108
references: 24188385
references: Hepatology. 2008 Jan;47(1):186-98
references: 17880014
references: Hepatology. 2006 Feb;43(2 Suppl 1):S45-53
references: 16447274
references: Biochem Biophys Res Commun. 2000 Jun 16;272(3):681-6
references: 10860814