The prevalence and purification of hepatoproliferin: a liver regeneration factor from rat hepatocytes

Hepatoproliferin (HPF), a liver regeneration factor that was able to augment the growth of hepatocytes in the presence of EGF, was produced by young rat livers and hepatectomized adult livers (70%), but not by adult intact livers. Therefore only growing and regenerating livers produce HPF. This growth factor was purified into two homogeneous bioactive species having different single SDS-PAGE bands at 18.5 and 14 kDa, and different single pI-bands at pH 4.3 and 8.7, respectively. HPF was synthesized de novo by hepatocytes in the liver as shown by the in vivo incorporation of radiolabeled 35S-sulfate and 14C/3H-glucosamine. This radioactive HPF was secreted ex vivo by hepatocytes, probably to act as an autocrinal hepatomitogen since 90% was found in the growth medium. HPF was neither a classical peptido-mitogen nor a heparin binding growth factor, but a liver-originated non-proteinaceous factor, which probably contains sulfonated saccharides such as glucosamine sulfate. HPF was neither a polyglycan nor a glycopeptide nor a peptidoglycan.