Response of sinusoidal mouse liver cells to choline-deficient ethionine-supplemented diet

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.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 traditional marker for identifying specific cell types. Thus, M2-pyruvate kinase should no longer be used for estimating the oval cell response in mouse liver. CDE diet leads to activation of GFAP positive HSCs in the pericentral zone of liver lobulus. In the periportal zone the detection of GFAP in biliary cells and oval cells, calls other cell types as progenitors of hepatocytes into question under CDE diet conditions.Oval cell reaction occurs under pathological conditions in human liver and in early stages of experimental hepatocarcinogenesis protocols in rodents provided hepatocyte proliferation is impaired. A frequently used protocol applies ethionine, the ethyl analogon of methionine, together with a choline deficient diet (CDE) [1]. During CDE diet many metabolic changes in hepatocytes take place leading to deposition of lipids in hepatocytes and massive lethal deterioration of this cell type. Surviving hepatocytes are no longer able to proliferate and to repopulate the damaged tissue. Instead, oval cells, the bipotential progenitor cells of liver that are resistant against the destroying mechanisms, are activated and enrich. For proliferation they require a typical microenvironment which is provided by cells of the hepatic sinusoids closely adjacent to them. The pivotal role of an intrahepatic inflammatory response in this process, and the recruitment of Kupffer cells and ot