EXPRESSION OF HEPATOCYTE GROWTH-FACTOR MESSENGER-RNA DURING OVAL CELLACTIVATION IN THE RAT-LIVER

The customary wave of hepatocyte regeneration which occurs in the rat liver after two-thirds partial hepatectomy can be abolished by oral ad ministration of the carcinogen 2-acetylaminofluorene. Instead, regener ation is achieved through the proliferation and differentiation of pot ential stem cells (oval cells) which appear to emanate from the portal space. Ultrastructural studies have illustrated the undifferentiated nature of these cells in the first 3 days after resection, but very ra pidly they acquire features of small hepatocytes or biliary epithelia. Oval cell progeny can form either cohesive columns of cells within si nusoids which may later differentiate into new hepatic plates, or sing le cells that can insinuate within existing plates. Using a S-35 antis ense riboprobe to hepatocyte growth factor (HGF) mRNA, the synthesis o f HGF mRNA was observed in sinusoid-lining cells. There were few HGF m RNA-expressing cells in the liver removed at resection, but numbers st eadily increased in the remnant over the next 7 days. In particular, a n almost nine-fold increase in the density of HGF mRNA-producing cells occurred in the periportal areas, resulting in approximately double t he density present within the centrilobular parenchyma. The superabund ance of HGF-producing cells in the immediate vicinity of oval cell pro liferation and differentiation strongly suggests that this growth fact or is involved in all aspects of stem cell behaviour-proliferation, mi gration, and differentiation, through a paracrine mechanism.