TGF‐β in Liver Development, Regeneration, and Carcinogenesisa

TGF-Pl is a potent inhibitor of hepatocyte DNA replication in culture.l.2This finding and the report.thata hepatocellular carcinoma cell line was not sensitive to DNA synthesis inhibition by TGF-P3 have led to a large number of studies to assess the role of E F -I , in normal and neoplastic liver growth and in the development of hepatic fibrosis.Here we present some of our studies on TGF-p during fetal, regenerative, and neoplastic growth in rat liver. FETAL DEVELOPMENT AND REGENERATIVE GROWTH TGF-pl mRNA in the Liver Fetal and Newborn LiverDuring fetal development there is a progressive decrease of TGF-PI mRNA in the liver from 15-days gestation until birth (FIG.1).Further decreases occur during the first three weeks of postnatal life and, at about 20 days, TGF-Pl mRNA is barely detectable in rat liver by conventional Northern blot analysis.This pattern differs from that of hepatic E F -a message.TGF-a mRNA increases in the liver during the first two postnatal weeks and decreases to very low levels by 20 days (FIG.1).In situ hybridization data4 indicate that TGF-P mRNA is localized in hemopoietic cells, although no detailed data are available on the localization of the message in hepatocyte precursors.The pattern of decrease of the E F -P message during fetal development and early postnatal life does not completely coincide with the timing of disappearance of hemopoietic cells from the liver.For TGF-a the message increase in this first two weeks of life coincides with a period of intense hepatocyte replication in newborn rats.An important point is that the amount of TGF-Dl mRNA in adult normal liver is extremely low, making it unlikely that E F -P l functions as a repressor that keeps hepatocytes quiescent in normal adult rats.