Stimulated synthesis of glycosaminoglycans in suspension cultures of hepatocytes from subacutely injured livers.

Parenchymal and nonparenchymal cells were isolated from normal and thioacetamide-injured rat livers, respectively. The cells were incubated in suspension cultures in the presence of [35S]-sulfate to study the synthesis of total and specific types of glycosaminoglycans. It is found that the production of total labeled glycosaminoglycans is stimulated about threefold in hepatocytes from liver injured for 2 days with a single intraperitoneal dose of thioacetamide (100 mg/kg b.w.) if compared to respective control cell incubations. Hepatocytes from rats injured for 2 months with thioacetamide also produced significantly more glycosaminoglycans than normal ones. In earlier stages of injury, i.e. 3 h after application of the drug, total glycosaminoglycan synthesis is depressed by about 40%. The pattern of glycosaminoglycans synthesized by hepatocytes from preinjured livers is changed in comparison to that of normal cells. The portion of HNO2-susceptible glycosaminoglycans (heparan sulfate) decreases whereas that of chondroitin ABC-lyase digestible material (chondroitin sulfate, dermatan sulfate) increases. Thus, synthesis and secretion of the latter types of glycosaminoglycans in suspension cultures of hepatocytes from subacutely injured livers are about 3-fold elevated. This fact indicates the possible fibrogenic potency of hepatocytes. Nonparenchymal cell incubations from normal and injured livers, respectively, were unable to incorporate any significant amount of [35S]-sulfate into glycosaminoglycans.