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

Abstract

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‐β). 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‐β. 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‐β in these cells were 250 pg/ml and 40 pg/ml, respectively. In contrast to TGF‐β the growth inhibitory activity of HPI was unaltered in the presence of an antibody raised against TGF‐β. The possible mechanism of action of HPI is discussed.