response of sinusoidal mouse liver cells to choline-deficient ethionine-supplemented diet回应的正弦小鼠肝细胞choline-deficient ethionine-supplemented饮食.pdfVIP

Ueberham et al. Comparative Hepatology 2010, 9:8 /content/9/1/8 RESEARCH Open Access Response of sinusoidal mouse liver cells to choline-deficient ethionine-supplemented diet 1* 1 2,4 3,4 1 Elke Ueberham , Jan Böttger , Uwe Ueberham , Jens Grosche , Rolf Gebhardt Abstract Background: Proliferation of oval cells, the bipotent precursor cells of the liver, requires impeded proliferation and loss of hepatocytes as well as a specific micro-environment, provided by adjacent sinusoidal cells of liver. Despite their immense importance for triggering the oval cell response, cells of hepatic sinusoids are rarely investigated. To elucidate the response of sinusoidal liver cells we have employed a choline-deficient, ethionine-supplemented (CDE) diet, a common method for inducing an oval cell response in rodent liver. We have utilised selected expression markers commonly used in the past for phenotypic discrimination of oval cells and sinusoidal cells: cytokeratin, E-cadherin and M2-pyruvate kinase for oval cells; and glial fibrillary acidic protein (GFAP) was used for hepatic stellate cells (HSCs). Results: CDE diet leads to an activation of all cells of the hepatic sinusoid in the mouse liver. Beside oval cells, also HSCs and Kupffer cells proliferate. The entire fraction of proliferating cells in mouse liver as well as endothelial cells and cholangiocytes express M2-pyruvate kinase. Concomitantly, GFAP, long considered a unique marker of quiescent HSCs was upregulated in activated HSCs and expressed also in cholangiocytes and oval cells. Conclusions: Our results point to an important role of all types of sinusoidal cells in regeneration from CDE induced liver damage and call for utmost caution in using