2 - Hepatocyte growth factor (HGF) and its receptor (Met) in liver regeneration, neoplasia, and disease

Abstract

This chapter emphasizes the aspects of the relationship between hepatocyte growth factor (HGF) and the liver that play a regulatory role in liver growth and function. Several past studies have demonstrated that between 1 and 2 h after partial hepatectomy, the plasma HGF level rapidly rises approximately 15–20 fold above of what is found in control animals. The rise in HGF is immediate and equally as sustained as after partial hepatectomy, but it is elevated for a longer period. Thus, in animals following a partial hepatectomy or CCI4 exposure, the rise in plasma HGF occurs rapidly and precedes the peak in hepatocyte DNA synthesis by approximately 20 to 24 h. In terms of a temporal correlation, the rise in HGF occurs during the time frame that is compatible with the induction in immediate early gene expression. Because plasma HGF level significantly increases in the peripheral blood, HGF is found to be compatible with the early findings documenting the rapid emergence of blood borne hepatotrophic factors following a partial hepatectomy. The role of HGF as a potential initiator of the hepatic regenerative process was further strengthened by recent studies that showed HGF stimulates the expression of some of the immediate early genes in the primary cultures of hepatocytes. A characteristic marker of this process is the liver regeneration factor, which is a transcription factor that functions similarly to I kappa B (IkB). Although liver regeneration factor (LRF) gene expression is stimulated in cultured hepatocytes by HGF, other factors, such as epidermal growth factor (EGF) also enhance the expression of LRF. This suggests that this effect of HGF is not specific, but rather relates to the overall initiation of hepatocyte growth.