Hepatocyte Growth Factor Accelerates Proliferation of Hepatic Oval Cells in a 2-Acetylaminofluorene/Partial Hepatectomy Model in the Rat

Abstract

In the rat, oval cells are thought to be hepatic stem-cell candidates. In humans, oval-like cells are also present in injured liver tissue, and are thought to play an important role in liver regeneration. The proliferation of oval cells in the liver in a 2-acetylaminofluorene/partial hepatectomy model in the rat was stimulated by treatment with hepatocyte growth factor (HGF), a major agent promoting the proliferation of mature hepatocytes. In the rat liver, periportal basophilic areas, consisting of oval cells, were significantly larger in rats treated with HGF than in those without HGF on day 7. Expressions of α-fetoprotein (AFP) and c-Kit were detected in the oval cells by immunohistochemistry. Enhanced expression of c-Met was also observed in the oval cells in comparison with the findings in surrounding mature hepatocytes; and tyrosine phosphorylation of c-Met in liver tissues was increased at 7 days of treatment with HGF. These results indicate that HGF promotes the proliferation of both mature hepatocytes and hepatic progenitor cells, and plays an important role in the regeneration of injured liver.