PMID- 21145821
OWN - NLM
STAT- MEDLINE
DCOM- 20110927
LR  - 20120824
IS  - 1600-0641 (Electronic)
IS  - 0168-8278 (Linking)
VI  - 54
IP  - 6
DP  - 2011 Jun
TI  - Vitamin D3 up-regulated protein 1 deficiency accelerates liver regeneration after 
      partial hepatectomy in mice.
PG  - 1168-76
LID - 10.1016/j.jhep.2010.09.025 [doi]
AB  - BACKGROUND & AIMS: 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 
      3beta (GSK3beta), 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-alpha. 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.
CI  - Copyright (c) 2010 European Association for the Study of the Liver. Published by 
      Elsevier B.V. All rights reserved.
FAU - Kwon, Hyo-Jung
AU  - Kwon HJ
AD  - Biomedical Mouse Resource Center, Korea Research Institute of Bioscience and 
      Biotechnology, Chungbuk, Republic of Korea.
FAU - Won, Young-Suk
AU  - Won YS
FAU - Yoon, Yeo-Dae
AU  - Yoon YD
FAU - Yoon, Won-Kee
AU  - Yoon WK
FAU - Nam, Ki-Hoan
AU  - Nam KH
FAU - Choi, In-Pyo
AU  - Choi IP
FAU - Kim, Dae-Yong
AU  - Kim DY
FAU - Kim, Hyoung-Chin
AU  - Kim HC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101026
PL  - Netherlands
TA  - J Hepatol
JT  - Journal of hepatology
JID - 8503886
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Cyclins)
RN  - 0 (HGF protein, mouse)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transforming Growth Factor alpha)
RN  - 0 (Txnip protein, mouse)
RN  - 52500-60-4 (Thioredoxins)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/antagonists & inhibitors/genetics/*physiology
MH  - Cell Cycle Proteins/metabolism
MH  - Cell Proliferation
MH  - Cell Size
MH  - Cyclins/metabolism
MH  - Hepatectomy
MH  - Hepatocyte Growth Factor/pharmacology
MH  - Hepatocytes/cytology/drug effects/metabolism
MH  - Liver Regeneration/genetics/*physiology
MH  - MAP Kinase Signaling System
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Signal Transduction
MH  - Thioredoxins/antagonists & inhibitors/genetics/*physiology
MH  - Transforming Growth Factor alpha/pharmacology
EDAT- 2010/12/15 06:00
MHDA- 2011/09/29 06:00
CRDT- 2010/12/15 06:00
PHST- 2010/03/11 00:00 [received]
PHST- 2010/08/24 00:00 [revised]
PHST- 2010/09/07 00:00 [accepted]
PHST- 2010/12/15 06:00 [entrez]
PHST- 2010/12/15 06:00 [pubmed]
PHST- 2011/09/29 06:00 [medline]
AID - S0168-8278(10)00928-1 [pii]
AID - 10.1016/j.jhep.2010.09.025 [doi]
PST - ppublish
SO  - J Hepatol. 2011 Jun;54(6):1168-76. doi: 10.1016/j.jhep.2010.09.025. Epub 2010 Oct 
      26.