Role of metalloproteinases at the onset of liver development.

At the onset of liver development, the hepatic precursor cells, namely, the hepatoblasts, derive from the ventral foregut endoderm and form a bud surrounded by a basement membrane (BM). To initiate liver growth, the hepatoblasts migrate across the BM and invade the neighboring septum transversum mesenchyme. In the present study, carried out in the mouse embryo, we searched for effectors involved in this process and we examined the role of matrix metalloproteinases (MMPs).

The Onecut transcription factors HNF-6/OC-1 and OC-2 regulate early liver expansion by controlling hepatoblast migration.

Liver development in mammals is initiated by the formation of a hepatic bud from the ventral foregut endoderm. The hepatic cells then proliferate and invade the septum transversum mesenchyme, and further differentiate to give rise to hepatocytes and biliary cells. By analyzing mice that are knockout for the transcription factors Hepatocyte Nuclear Factor-6 (HNF-6)/Onecut-1 (OC-1) and OC-2, we show here that these factors redundantly stimulate the degradation of the basal lamina surrounding the liver bud and promote hepatoblast migration in the septum transversum.

Kupffer cell-derived prostaglandin E2 is involved in regulation of lipid synthesis in rat liver tissue.

Our recent studies suggest that Kupffer cells play a role in the physiological regulation of lipid metabolism of the adjacent hepatocytes. In the present study, we have tested the hypothesis that inhibition of Kupffer cells decreases prostaglandin E(2) (PGE(2)) release inside liver tissue, a phenomenon contributing to lipid accumulation in hepatocytes. PGE(2) secretion as well as lipid synthesis were assessed in precision-cut liver slices (PCLS) from rats previously treated with Kupffer cell inhibitors (GdCl(3) 10 mg kg(-1) body wt, i.