Collagen synthesis by the hepatocyte: studies in primary cultures of parenchymal cells from adult rat liver.
Based on the finding that prolyl hydroxylase, a key enzyme in collagen biosynthesis, is a constituent of the hepatic parenchymal cell, we have suggested that the hepatocyte may synthesize collagen (Exp. Cell Res. 123: 269-279, 1979). We now report that, consistent with this idea, collagen formation has been detected in primary nonproliferating cultures of isolated rat hepatocytes prepared from either normal liver or regenerated liver four days after partial hepatectomy. The characteristics of the radiolabeled collagen formed in two-day old cultures incubated for 24 hours in the presence of either [3H]-proline or [35S]-cystine were its resistance to pepsin and its susceptibility to degradation by highly purified, protease-free bacterial collagenase. The presence of fibroblasts in the hepatocyte cultures was excluded as an explanation for these results because we detected no type I collagen, a universal product of the cultured fibroblast. The initial low rates of synthesis of collagen relative to total cellular protein (0.1-0.4 percent) increased dramatically upon continued incubation of the cells reaching 0.31 and 0.81 percent in nine-day old cultures of normal or regenerated hepatocytes, respectively. This change was accompanied by the synthesis of an additional 100,000 molecular weight from of collagen, possibly type I or A, B. Morphologically, the hepatocytes progressively flattened and overlapped adjacent cells with time in culture. However, their identify as hepatocytes was confirmed by the fact that synthesis of fibrinogen, a liver-specific function, was maintained above initial levels throughout the experiment. We conclude that synthesis of collagen is a constitutive function of the hepatocyte. This function is linked to hepatocyte replication, is subject to phenotypic change in culture, and may be important in the pathogenesis of hepatic fibrosis or cirrhosis.
D000367:Age Factors; D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D005340:Fibrinogen / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008115:Liver Regeneration; D051381:Rats
D005340:Fibrinogen; D003094:Collagen