Hepatokines are autocrine or paracrine growth factors for liver tissue. The hepatopoietin described in this application is a novel hepatocyte-specific, growth factor. In preliminary work, hepatopoietin was purified to homogeneity (based on SDS-PAGE, reverse phase HPLC and capillary electrophoresis) and found to have a blocked N-terminus. Amino acid composition and physical properties indicate that this protein has not been previously described. Highly purified hepatopoietin administered after a lethal dose of carbon tetrachloride protected the exposed mice. Serum enzymes indicate a protective effect on hepatocytes. Sufficient partially purified hepatopoietin is available to prepare fragments to obtain internal peptide sequences. Preparation of antibodies is underway. Thus the phase I goals are to use either oligonucleotide probes or antibodies to clone the cDNA from a commercially available fetal liver cDNA library. In phase II the hepatopoietin will be expressed, purified and tested in various models of hepatic injury. Unlike previously described hepatokines and hepatocyte growth factors, hepatopoietin is a specific hepatocyte growth factor. Therefore hepatopoietin promises to be an interesting and important hepatokine, with diagnostic and therapeutic potential in a variety of liver diseases.
