The Role of Fibroblast Activation Protein in Chronic Liver Injury

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Chronic liver diseases, particularly those caused by Hepatitis B virus and Hepatitis C virus infection, are major causes of morbidity and mortality in our community. They are characterised by progressive scarring of the liver which finally leads to liver failure and the need in many cases for organ transplantation. We have identified a key molecule Fibroblast Activation Protein (FAP) that may play a key role and the process of liver fibrosis (scarring). The aims of the project are four fold: (1) To characterise where and on what cells FAP is produced in the liver and whether FAP levels correlate with the development of fibrosis in human chronic liver diseases caused by either Hepatitis B or Hepatitis C virus infections. (2) To examine a mouse strain in which the FAP molecule is knocked out ie absent. This will tell us whether FAP itself is essential for the development of fibrosis. (3) To isolate the cells within the liver that make FAP and to examine how particular functions of these cells are modified by FAP. (4) To find out what particular molecules FAP acts upon to perform its functions. The achievement of these aims will greatly increase our understanding of this key enzyme and its role in chronic liver injury. This work can potentially lead to the development of specific inhibitors of FAP function designed to relieve liver damage.