Transforming growth factor beta mRNA increases during liver regeneration: a possible paracrine mechanism of growth regulation.

Abstract

Transforming growth factor .beta. (TGF-.beta.) is a growth factor with multiple biological properties including stimulation and inhibition of cell proliferation. To determine whether TGF-.beta. is involved in hepatocyte growth responses in vivo, we measured the levels of TGF-.beta. mRNA in normal liver and during liver regeneration after partial hepatectomy in rats. TGF-.beta. mRNA increases in the regenerating liver and reaches a peak (about 8 times higher than basal levels) after taken place and after the peak expression of the ras protooncogenes. Although hepatocytes from normal and regenerating liver respond to TGF-.beta., they do not synthesize TGF-.beta. mRNA. Instead, the message is present in liver nonparenchymal cells and is particularly abundant in cell fractions enriched for endothelial cells. TGF-.beta. inhibits epidermal growth factor-induced DNA synthesis in vitro in hepatocytes from normal and regenerating liver, although the dose-response curves vary according to the culture medium used. We conclude that TGF-.beta. may function as the effector of an inhibitory paracrine loop that is activated during liver regeneration, perhaps to prevent uncontrolled hepatocyte proliferation.