PMID- 24390087
OWN - NLM
STAT- MEDLINE
DCOM- 20141103
LR  - 20211021
IS  - 1573-4919 (Electronic)
IS  - 0300-8177 (Linking)
VI  - 389
IP  - 1-2
DP  - 2014 Apr
TI  - Sustained endoplasmic reticulum stress inhibits hepatocyte proliferation via 
      downregulation of c-Met expression.
PG  - 151-8
LID - 10.1007/s11010-013-1936-8 [doi]
AB  - The molecular mechanisms of impaired liver regeneration in several liver diseases 
      remain poorly understood. Endoplasmic reticulum (ER) stress has been observed in 
      a variety of liver diseases. The aims of this study were to explore the impacts 
      of ER stress on hepatocyte growth factor (HGF)-induced proliferation and c-Met 
      expression in human hepatocyte L02 cells. Human hepatocyte L02 cells were 
      incubated with thapsigargin (TG) to induce ER stress. 4-Phenylbutyric acid (PBA) 
      was used to rescue ER stress. Activation of glucose-regulated protein 78, 
      phosphorylation of PKR-like ER kinase and eukaryotic translation initiation 
      factor-2alpha, and the expression of c-Met were determined by western blotting. The 
      expression of c-Met mRNA was observed by reverse transcription polymerase chain 
      reaction. L02 cell proliferation was determined by the MTS assay. L02 cell 
      proliferation was significantly impaired in TG-treated L02 cells from 24 to 48 h, 
      while PBA partly restored the proliferation of L02 cells. In addition, TG 
      treatment significantly decreased the sensitivity of L02 cells to HGF-induced 
      proliferation. PBA partly resumed the sensitivity of L02 cells to HGF-induced 
      proliferation. The expression of c-Met protein in L02 cells was downregulated 
      from 6 h after TG treatment, and PBA partly restored c-Met expression inhibited 
      by TG. The expression of c-Met mRNA was also significantly downregulated from 24 
      to 48 h after TG treatment. Our results strongly suggest that sustained ER stress 
      inhibits hepatocyte proliferation via downregulation of both c-Met mRNA and 
      protein expression in human hepatocyte L02 cells.
FAU - He, Yihuai
AU  - He Y
AD  - Department of Infectious Diseases, Zunyi Medical College, 201 Dalian Street, 
      Zunyi, 563003, Guizhou, China.
FAU - Long, Jun
AU  - Long J
FAU - Zhong, Weiwei
AU  - Zhong W
FAU - Fu, Yu
AU  - Fu Y
FAU - Li, Ying
AU  - Li Y
FAU - Lin, Shide
AU  - Lin S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140105
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (HSP70 Heat-Shock Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (glucose-regulated proteins)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Cell Line
MH  - Cell Proliferation
MH  - Down-Regulation/*genetics
MH  - Endoplasmic Reticulum Stress/*genetics
MH  - Gene Expression/*genetics
MH  - HSP70 Heat-Shock Proteins/genetics
MH  - Hepatocyte Growth Factor/genetics
MH  - Hepatocytes/*metabolism
MH  - Humans
MH  - Membrane Proteins/genetics
MH  - Phosphorylation/genetics
MH  - Proto-Oncogene Proteins c-met/*genetics
EDAT- 2014/01/07 06:00
MHDA- 2014/11/05 06:00
CRDT- 2014/01/07 06:00
PHST- 2013/08/01 00:00 [received]
PHST- 2013/12/18 00:00 [accepted]
PHST- 2014/01/07 06:00 [entrez]
PHST- 2014/01/07 06:00 [pubmed]
PHST- 2014/11/05 06:00 [medline]
AID - 10.1007/s11010-013-1936-8 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2014 Apr;389(1-2):151-8. doi: 10.1007/s11010-013-1936-8. Epub 
      2014 Jan 5.