Transforming growth factor beta and inhibition of hepatocellular proliferation.

Transforming growth factor beta (TGF beta) is a recently characterized polypeptide that elicits diverse biologic actions in a wide range of cell types in vitro. TGF beta is a bifunctional growth regulator of fibroblasts with either growth stimulation or growth inhibition but inhibits the growth of most epithelial cells. In addition, TGF beta can either block or induce the differentiation of certain cells. TGF beta reversibly inhibits DNA synthesis in normal adult rat hepatocytes and in cells isolated from regenerating liver 12 h and 18 h after partial hepatectomy. However, at 3 h and 6 h after hepatectomy there is a decrease in sensitivity of hepatocytes to growth inhibition by TGF beta. Recent data from other laboratories indicate that TGF beta expression increases substantially in liver after partial hepatectomy and that administration of purified TGF beta in vivo inhibits DNA synthesis in regenerating rat liver. Together with our observations, these findings suggest that TGF beta may play a central role as a negative paracrine growth regulator in adult rat liver.