Trautwein C, Davies M, Elias E, Strain A, Manns M P
Abteilung Gastroenterologie und Hepatologie, Medizinische Hochschule Hannover, Germany.
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.
细胞外基质蛋白对人类肝脏特异性基因表达的作用已得到研究。细胞色素P450 2D6和白蛋白是在肝细胞中组成性表达的两个肝脏特异性基因。原代人肝细胞在不同的细胞外基质蛋白上培养，即胶原蛋白、纤连蛋白、胶原蛋白/纤连蛋白组合以及富含EHS层粘连蛋白的凝胶，并在不同的培养条件下培养。培养48小时后，原代人肝细胞的DNA合成出现峰值，同时白蛋白和P450 2D6的肝脏特异性表达下调，表明肝细胞去分化。随后肝脏特异性基因的分化和表达开始增加。与接种在富含EHS层粘连蛋白的凝胶、胶原蛋白或胶原蛋白与纤连蛋白组合上的细胞相比，如果肝细胞接种在纤连蛋白上，由白蛋白和P450 2D6水平确定的再分化更为明显。
