Liver growth and regeneration, and the expression of growth-related genes, were studied in Mrp3+/+ and Mrp3??/sup> mice fed a cholic acid (CA) supplemented diet and after 2/3 PH. Activation of the BA receptor FXR was measured in mice after in vivo transduction of the liver with a FXR-Luciferase reporter plasmid. BA levels were measured in portal serum and liver tissue by high performance liquid chromatography-tandem mass spectrometry. Liver growth elicited by CA feeding was significantly reduced in Mrp3??/sup> mice. These animals showed reduced FXR activation in the liver after CA administration and decreased portal serum levels of BA. Liver regeneration after PH was significantly delayed in Mrp3-deficient mice. Proliferation-related gene expression and peak DNA synthesis in Mrp3??/sup> mice occurred later than in wild types, coinciding with a retarded elevation in intra-hepatic BA levels. Lack of Abcc3 expression markedly impairs liver growth in response to BA and after PH. Our data suggest that Mrp3 plays a non-redundant role in the regulation of BA flux during liver regeneration.Results
Conclusions