Extracellular matrix proteins modulate cytochrome P450 2D6 expression in human hepatocytes

J Hepatol. 1995 Jan;22(1):50-6. doi: 10.1016/0168-8278(95)80259-2.


The role of extracellular matrix proteins on the expression of human liver-specific genes has been investigated. Cytochrome P450 2D6 and albumin are two liver-specific genes which are constitutively expressed in hepatocytes. Primary human hepatocytes were cultured on different extracellular matrix proteins, namely collagen, fibronectin, a combination of collagen/fibronectin and EHS-laminin rich gel, and under different culture conditions. After 48 h in culture, primary human hepatocytes showed a peak in DNA-synthesis associated with a downregulation of liver-specific expression of albumin and P450 2D6, indicating the dedifferentiation of the hepatocytes. Differentiation and expression of liver-specific genes started to increase subsequently. Redifferentiation as determined by albumin and P450 2D6 levels was more pronounced if hepatocytes were seeded on fibronectin, compared to cells seeded on EHS-laminin rich gel, collagen or a combination of collagen and fibronectin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Cells, Cultured
  • Cytochrome P-450 CYP2D6
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism
  • DNA / biosynthesis
  • Extracellular Matrix Proteins / physiology*
  • Gene Expression Regulation*
  • Humans
  • Liver / cytology
  • Liver / physiology*
  • Mixed Function Oxygenases / genetics*
  • Mixed Function Oxygenases / metabolism
  • RNA, Messenger / metabolism
  • Serum Albumin / metabolism


  • Extracellular Matrix Proteins
  • RNA, Messenger
  • Serum Albumin
  • DNA
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • Cytochrome P-450 CYP2D6