iTRAQ-Based Membrane Proteomics Reveals Plasma Membrane Proteins Change During HepaRG Cell Differentiation

J Proteome Res. 2016 Dec 2;15(12):4245-4257. doi: 10.1021/acs.jproteome.6b00305. Epub 2016 Nov 10.


HepaRG cell, a stabilized bipotent liver progenitor cell line, exhibits hepatocyte functions only after differentiation. However, the mechanism of transition from nondifferentiated to differentiated states, accompanied by proliferation migration and differentiation, remains poorly understood, particularly those proteins residing in the plasma membrane. In this study, the membrane protein expression change of HepaRG cell during differentiation were systematically analyzed using an iTRAQ labeled quantitative membrane proteomics approach. A total of 70 membrane proteins were identified to be differentially expressed among 849 quantified membrane proteins. Function and disease clustering analysis proved that 11 of these proteins are involved in proliferation, migration, and differentiation. Two key factors (MMP-14 and OCLN) were validated by qRT-PCR and Western blot. Blockade of MMP-14 further demonstrated its important function during tumor cell migration. The data sets have been uploaded to ProteomeXchange with the identifier PXD004752.

Keywords: HPCs; HepaRG; MMP-14; iTRAQ; membrane protein; migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Differentiation*
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cluster Analysis
  • Gene Expression Regulation
  • Hepatocytes / cytology
  • Humans
  • Matrix Metalloproteinase 14 / analysis*
  • Membrane Proteins / analysis*
  • Membrane Proteins / physiology
  • Occludin / analysis*
  • Proteomics / methods*


  • Membrane Proteins
  • OCLN protein, human
  • Occludin
  • Matrix Metalloproteinase 14