Molecular and Cellular Biochemistry

, Volume 389, Issue 1–2, pp 151–158 | Cite as

Sustained endoplasmic reticulum stress inhibits hepatocyte proliferation via downregulation of c-Met expression

  • Yihuai He
  • Jun Long
  • Weiwei Zhong
  • Yu Fu
  • Ying Li
  • Shide Lin


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-2α, 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.


Hepatocyte Hepatocyte growth factor Proliferation Endoplasmic reticulum stress c-Met 



This work was partially supported by the Funds of the Chinese National Natural Science Foundation Project (81160067/H0318).


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Yihuai He
    • 1
  • Jun Long
    • 1
  • Weiwei Zhong
    • 1
  • Yu Fu
    • 1
  • Ying Li
    • 1
  • Shide Lin
    • 1
  1. 1.Department of Infectious DiseasesZunyi Medical CollegeZunyiChina

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