The Role of Hepatocyte Growth Factor in Liver Disease and Liver Regeneration

Hepatocyte growth factor (HGF) is a novel protein which is believed to have an important role in liver regeneration. Initially identified as the most potent mitogen for cultured hepatocytes, levels of HGF have since been shown to be elevated in serum and liver in animal models of liver disease. Raised levels have also been reported in serum from patients with liver disease. The receptor for HGF has been identified as the c-met proto-oncogene product. Although much has been learned of the structure and function of HGF in vitro, the significance of HGF and its receptor in controlling liver growth in health and disease remains to be determined. The work of this thesis represents my attempts to investigate the significance of HGF in human liver disease and in an animal model of liver regeneration. The aims of this work were as follows; (1) Production of recombinant proteins based on human and rat HGF in order to to raise antibodies to native HGF. (2) Purification of native human HGF in order to produce monoclonal and polyclonal antibodies to HGF. (3) To establish an Enzyme Linked Immunosorbent Assay (ELISA) to measure serum HGF in patients with various liver diseases and to correlate these levels with disease type and severity. (4) Immunocytochemical localisation of HGF and its receptor in human liver biopsies. (5) Examination of the expression of HGF mRNA in human liver biopsies by in situ hybridisation techniques. (6) Modification of the hepatic regenerative response to experimental liver injury by administration of neutralising anti-HGF antibody. (Abstract shortened by ProQuest.)