title: Vitamin D3 up-regulated protein 1 deficiency accelerates liver regeneration after partial hepatectomy in mice.
abstract: OBJECTIVE
  Liver regeneration is a complicated process involving a variety of interacting factors. Vitamin D3 up-regulated protein 1 (VDUP1) is a potent growth suppressor that, upon over-expression, inhibits tumor cell proliferation and cell-cycle progression. Here, we investigated the function of VDUP1 in liver regeneration following hepatectomy in mice.
  
  
  METHODS
  Liver regeneration after 70% partial hepatectomy (PH) was compared in VDUP1 knockout (KO) and wild-type (WT) mice, and the activities of proliferative- and cell-cycle-related signaling pathways were measured.
  
  
  RESULTS
  Compared with WT mice, liver recovery was significantly accelerated in VDUP1 KO mice during the first day after PH, in association with increased DNA synthesis. Consistent with this observation, the expression levels of key cell-cycle regulatory proteins, including cyclin D, cyclin E, cyclin-dependent kinase 4 (CDK4), p21, and p27, were markedly altered in the livers of VDUP1 KO mice. Induction of growth factors and activation of proliferative signaling pathway components including extracellular signal-regulated kinase 1/2 (ERK1/2), Akt, glycogen synthase kinase 3β (GSK3β), mammalian target of rapamycin (mTOR), and p70S6 kinase (p70(S6K)), occurred much earlier and to a greater extent in VDUP1 KO mouse livers. In addition, primary hepatocytes isolated from VDUP1 KO mice displayed increased activation of ERK1/2 and Akt in response to HGF and TGF-α.
  
  
  CONCLUSIONS
  Our results reveal an important role for VDUP1 in the regulation of proliferative signaling during liver regeneration. Altered activation of genes involved in ERK1/2 and Akt signaling pathways may explain the accelerated growth responses seen in VDUP1 KO mice.
authors.affiliation: Biomedical Mouse Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk, Republic of Korea.
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Young-Suk
authors.initials: YS
authors.lastname: Won
authors.forename: Yeo-Dae
authors.initials: YD
authors.lastname: Yoon
authors.forename: Won-Kee
authors.initials: WK
authors.lastname: Yoon
authors.forename: Ki-Hoan
authors.initials: KH
authors.lastname: Nam
authors.forename: In-Pyo
authors.initials: IP
authors.lastname: Choi
authors.forename: Dae-Yong
authors.initials: DY
authors.lastname: Kim
authors.forename: Hyoung-Chin
authors.initials: HC
authors.lastname: Kim
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D048429:Cell Size; D016213:Cyclins / Q000378:metabolism; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008115:Liver Regeneration / Q000235:genetics / Q000502:physiology*; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013879:Thioredoxins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D016211:Transforming Growth Factor alpha / Q000494:pharmacology
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; C553307:HGF protein, mouse; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; C445672:Txnip protein, mouse; D013879:Thioredoxins; D017228:Hepatocyte Growth Factor; D051057:Proto-Oncogene Proteins c-akt