Hepatocyte collagen production in vivo in normal rats

Although hepatocytes produce collagen in vitro, their contribution to hepatic collagen synthesis in vivo is unknown. To answer this question, we injected rats intraperitoneally with [3H]proline and [14C]ornithine. [3H]Proline labeled prolyl-t-RNA in both hepatocytes and nonparenchymal cells. In contrast, [14C]ornithine was rapidly converted to [14C]arginine via the urea cycle only in hepatocytes, labeling arginyl-t-RNA. Approximately 60% of the 14C in albumin and transferrin was present as arginine while the remainder was found in proline and related amino acids. As expected for proteins that have the same proline/arginine ratio and that are produced solely by the hepatocyte, the [3H]proline/[14C]arginine ratio was very similar in albumin and transferrin. Conversely, in nonparenchymal cells a negligible percentage of 14C was present as arginine. A sizeable percentage of the 14C in hepatic collagen was present as arginine; given the greater proline(+hydroxyproline)/arginine ratio in hepatic collagen, our data indicate that in normal rats, hepatocytes contribute most of newly synthesized hepatic collagen.