Characterization of a hepatic proliferation inhibitor (HPI): effect of HPI on the growth of normal liver cells--comparison with transforming growth factor beta.

Improvements in the purification of a hepatic proliferation inhibitor (HPI) from adult rat liver have yielded a product that has an inhibitory activity 1,000-fold greater than previously reported. The growth inhibitory activity, which could be eluted from SDS-PAGE at 17-19 kilodaltons (kD), was compared to that of transforming growth factor beta (TGF-beta). The ID50 of the HPI preparation in Fischer rat liver epithelial cells was 50 pg/ml (2.5 pM) compared to a value of 260 pg/ml (10.4 pM) obtained for pure human TGF-beta. Both inhibitors also modulated the stimulation of DNA synthesis in primary hepatocytes by either epidermal growth factor or a growth stimulatory activity prepared from serum of hepatectomized rats. The ID50s of HPI and TGF-beta in these cells were 250 pg/ml and 40 pg/ml, respectively. In contrast to TGF-beta the growth inhibitory activity of HPI was unaltered in the presence of an antibody raised against TGF-beta. The possible mechanism of action of HPI is discussed.