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

✍ Scribed by Jorge Cerbón-Ambriz; Jorge Cerbón-Solórzano; Marcos Rojkind

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 697 KB
• Volume: 13
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840130324

✦ Synopsis

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 CC1,-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 SH-proline into protein-bound SH-hydroqproline is increased threefold to fourfold in hepatocytes from CC1,-treated rats as compared with normal rat hepatocytes; (b) neither the hepatocytes from normal nor those from CC1,-treated rats modify their collagen synthesizing capacity when 30 mmoUL lactic acid was added to the incubation medium; (c) nonparenchymal cells obtained from livers of CC1,-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;13:651-666.)

The normal response of the liver to an acute injury is to regenerate (1). If regulation of the regenerative process is altered, as occurs in chronic injury, fibrous scar tissue accumulates. The factors that participate in the transformation of the hepatic response from regeneration to scar formation remain unclear (2). Various cells within the normal liver have been shown to produce collagen. Fat-storing (Ito) cells (FSC) produce collagen type I and type I11 (3). Additional collagen-synthesizing cells, such as myofibroblasts, could be recruited from the vessels during injury (4) or could be derived from FSC