Transforming Growth Factor β and Inhibition of Hepatocellular Proliferation

Abstract

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

Key Words:

• Growth inhibitor
• hepatocytes
• liver regeneration
• transforming growth factor β