Extracellular matrix proteins modulate cytochrome P450 2D6 expression in human hepatocytes.
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.
Trautwein
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C
Abteilung Gastroenterologie und Hepatologie, Medizinische Hochschule Hannover, Germany.
Davies
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M
Elias
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E
Strain
A
A
Manns
M P
MP
D015152:Blotting, Northern; D002478:Cells, Cultured; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000166:cytology / Q000502:physiology*; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism
D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D012709:Serum Albumin; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6