Stimulation of albumin synthesis in rat hepatocytes by ascites from patients with cirrhosis.

Hepatocyte growth factor (HGF), identified in ultrafiltered ascites and plasma from patients with cirrhosis, enhances the DNA synthesis in adult rat hepatocytes cultured at low cell density. This study was carried out to investigate the effect of ascites and plasma from patients with cirrhosis on liver-specific functions such as albumin synthesis in adult rat hepatocytes cultured at confluent-cell density. Ultrafiltered ascites from patients with cirrhosis and its ascitic protein, partially purified by fractionation with ammonium sulfate and gel filtration on Sephadex G-200, stimulated albumin synthesis in a dose-dependent manner in the presence of 10(-8), M dexamethasone. This effect was greater than that of 10(-7) M insulin and similar to that of 10(-7) M dexamethasone, but was additive with that of insulin plus dexamethasone. The molecular weight of the ascitic factor was estimated as 100,000 to 150,000, corresponding to that of HGF purified from cirrhotic ascites. Moreover, the partially purified ascitic factor markedly stimulated DNA and protein synthesis in hepatocytes. These findings suggest that the ascitic factor may act as HGF by stimulating hepatocyte DNA and albumin synthesis in a cell density-dependent manner.