Foetal rise in hepatic enzymes follows decline in c-met and hepatocyte growth factor expression

Background/Aims: In the embryo, rapidly proliferating hepatocytes migrate f rom the liver primordium into the surrounding mesenchyme, whereas foetal he patocytes are mitotically quiescent and accumulate hepatocyte-specific enzy mes. We investigated the timing and topography of this behavioural switch. Methods: The expression of the c-met receptor and its ligand, hepatocyte gr owth factor (HGF), was investigated in prenatal rat liver by in situ hybrid ization, immunohistochemistry and western-blot analysis. Results: c-Met was expressed by hepatocytes and HGF by non-parenchymal live r cells. Their mRNA levels peaked during embryonic day (ED) 11-13. c-Met pr otein was weakly expressed in the entire liver during ED 11 and 12, but mor e abundantly at ED 13, when its expression withdrew to the hepatic peripher y. Simultaneously, the periportal hepatocellular marker carbamoylphosphate synthetase began to accumulate in the centre of the liver. Although the def initive vascular architecture develops simultaneously, the downstream, peri central hepatocytes began to express glutamine synthetase only 4 days later , suggesting a requirement for prior periportal hepatocyte maturation. Addi tionally, c-met protein appeared in the connective tissue surrounding the l arge veins. The c-met protein/mRNA ratio was substantially higher in non-ep ithelial cells (hepatic connective tissue, heart) than in endoderm-derived epithelia, including hepatocytes, indicating important post-transcriptional regulation. Conclusion: The decline in c-met expression reflects the end of the embryon ic phase and heralds the onset of the fetal, maturational phase of liver de velopment. (C) 2001 European Association for the Study of the Liver. Publis hed by Elsevier Science B.V. All rights reserved.