01992 Raven Press, Ltd., New York
J Clin Gastroenterol 1992;15(1):64-8.
Basic Science in Gastroenterology Basil Rigas, Editor
Pathogenesis of Hepatic Fibrosis and the Role of Cytokines Trevor W. Lissoos,
M.D.,
and Bernard H. Davis,
No definitive therapy exists for the treatment of hepatic fibrosis and cirrhosis. Recent evidence suggests that hepatic lipocytes (It0 cells, fat storage cells, or stellate cells of the liver) are responsible for much of the collagen hypersecretion and nodule formation that occurs during hepatic fibrosis and cirrhosis. This review describes the cellular mechanisms of hepatic fibrogenesis emphasizing new experimental data about cytokines or growth factors to suggest potential avenues of future therapeutic design. Key Words: Liver diseases-Cirrhosis-Fibrosis-Qtokines.
M.D.
Hepatic fibrosis is a consequence of severe liver damage, occurring in many chronic liver diseases as a forerunner to cirrhosis (1-3). In fibrosis, the liver structure is preserved. In cirrhosis, the liver architecture is disrupted with fibrous bands of connective tissue bridging portal and central areas with the formation of “regenerative” nodules (1-3). Various agents including corticosteroids, penicillamine, and colchicine have been used in the therapy of hepatic fibrosis, but no therapy is established (4).In this brief review of hepatic fibrogenesis, we will emphasize new experimental data about regulatory factors to suggest potential avenues of future therapeutic design.
THE NORMAL LIVER Connective tissues are defined as the extracellular components that provide the structural support of the body and bind together its cells, tissues, and organs (5). Like all organs, the liver contains connective tissue, often referred to as the extracellular matrix. This extracellular matrix is composed of collagens, glycosylated proteins, and proteins with sulfated polysaccharide side chains referred to as proteoglycans. The collagens comprise a family of 15 district proteins, some of which are characterized by a triple helical structure (6). They represent the major component of the extracellular matrix (6). Each collagen has a characteristic structure, tissue distribution, and a unique biologic function in forming either fibrils or network-like structures (5). Collagen types I, 111, IV, V, and VI are present in the normal liver (4). Type I and I11 collagens are present in approximately equal amounts in the liver, constituting about 80% of total hepatic collagen (4,7).
From the Gastroenterology Section, Department of Medicine, University of Chicago, Chicago, Illinois, U.S.A. Address correspondence and reprint requests to Dr. Bernard H. Davis, Gastroenterology Section, Department of Medicine, University of Chicago Medical Center, Box 400, 5841 South Maryland Avenue, Chicago, IL 60637, U.S.A.
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J Clin Gastroenterol 1992;15(1):64-8.
Basic Science in Gastroenterology Basil Rigas, Editor
Pathogenesis of Hepatic Fibrosis and the Role of Cytokines Trevor W. Lissoos,
M.D.,
and Bernard H. Davis,
No definitive therapy exists for the treatment of hepatic fibrosis and cirrhosis. Recent evidence suggests that hepatic lipocytes (It0 cells, fat storage cells, or stellate cells of the liver) are responsible for much of the collagen hypersecretion and nodule formation that occurs during hepatic fibrosis and cirrhosis. This review describes the cellular mechanisms of hepatic fibrogenesis emphasizing new experimental data about cytokines or growth factors to suggest potential avenues of future therapeutic design. Key Words: Liver diseases-Cirrhosis-Fibrosis-Qtokines.
M.D.
Hepatic fibrosis is a consequence of severe liver damage, occurring in many chronic liver diseases as a forerunner to cirrhosis (1-3). In fibrosis, the liver structure is preserved. In cirrhosis, the liver architecture is disrupted with fibrous bands of connective tissue bridging portal and central areas with the formation of “regenerative” nodules (1-3). Various agents including corticosteroids, penicillamine, and colchicine have been used in the therapy of hepatic fibrosis, but no therapy is established (4).In this brief review of hepatic fibrogenesis, we will emphasize new experimental data about regulatory factors to suggest potential avenues of future therapeutic design.
THE NORMAL LIVER Connective tissues are defined as the extracellular components that provide the structural support of the body and bind together its cells, tissues, and organs (5). Like all organs, the liver contains connective tissue, often referred to as the extracellular matrix. This extracellular matrix is composed of collagens, glycosylated proteins, and proteins with sulfated polysaccharide side chains referred to as proteoglycans. The collagens comprise a family of 15 district proteins, some of which are characterized by a triple helical structure (6). They represent the major component of the extracellular matrix (6). Each collagen has a characteristic structure, tissue distribution, and a unique biologic function in forming either fibrils or network-like structures (5). Collagen types I, 111, IV, V, and VI are present in the normal liver (4). Type I and I11 collagens are present in approximately equal amounts in the liver, constituting about 80% of total hepatic collagen (4,7).
From the Gastroenterology Section, Department of Medicine, University of Chicago, Chicago, Illinois, U.S.A. Address correspondence and reprint requests to Dr. Bernard H. Davis, Gastroenterology Section, Department of Medicine, University of Chicago Medical Center, Box 400, 5841 South Maryland Avenue, Chicago, IL 60637, U.S.A.
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