Regulation of collagen production in freshly isolated cell populations from normal and cirrhotic rat liver: Effect of lactate

Authors

  • Jorge Cerbón-Ambriz,

    1. Department of Biochemistry, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City, Mexico 07000
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  • Jorge Cerbón-Solórzano,

    1. Department of Biochemistry, Centro de Investigación y de Estudios Avanzados del IPN, Mexico City, Mexico 07000
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  • Marcos Rojkind M.D., Ph.D.

    Corresponding author
    1. Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461
    • Professor of Medicine and Pathology, Liver Research Center, U-625, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461
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Abstract

Previous work has shown that lactic acid, and to a lesser extent pyruvic acid, is able to increase collagen synthesis significantly in liver slices of CCl4-treated rats but not normal rats. The purpose of this report is to document which cells in the cirrhotic liver are responsible for the lactate-stimulated increase in collagen synthesis. It was found that (a) incorporation of 3H-proline into protein-bound 3H-hydroxyproline is increased threefold to fourfold in hepatocytes from CCl4-treated rats as compared with normal rat hepatocytes; (b) neither the hepatocytes from normal nor those from CCl4-treated rats modify their collagen synthesizing capacity when 30 mmol/L lactic acid was added to the incubation medium; (c) nonparenchymal cells obtained from livers of CCl4-treated rats synthesize much less collagen than hepatocytes, but their synthesis is stimulated twofold by lactic acid; (d) from the different nonparenchymal cells, only fat-storing (Ito) cells increase collagen synthesis when lactic acid is present in the incubation medium. These results suggest that the increased lactic acid levels observed in patients with alcoholic hepatic cirrhosis may play an important role in the development of fibrosis by stimulating collagen production by fat-storing (Ito) cells. (HEPATOLOGY 1991;13:551–556.)

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