What's new in liver fibrosis? The origin of myofibroblasts in liver fibrosis

Authors

  • Keiko Iwaisako,

    1. Department of Medicine, University of California, San Diego, La Jolla, California, USA
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  • David A Brenner,

    Corresponding author
    1. Department of Medicine, University of California, San Diego, La Jolla, California, USA
      Professor David A Brenner, Division of Gastroenterology, Department of Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive #0602, Biomedical Sciences Building 1318, La Jolla, CA 92093-0602, USA. Email: dbrenner@ucsd.edu
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  • Tatiana Kisseleva

    1. Department of Medicine, University of California, San Diego, La Jolla, California, USA
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  • Conflict of Interests: There are no conflicts of interests.

Professor David A Brenner, Division of Gastroenterology, Department of Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive #0602, Biomedical Sciences Building 1318, La Jolla, CA 92093-0602, USA. Email: dbrenner@ucsd.edu

Abstract

Chronic liver injury of many etiologies produces liver fibrosis and may eventually lead to the formation of cirrhosis. Fibrosis is part of a dynamic process associated with the continuous deposition and resorption of extracellular matrix, mainly fibrillar collagen. Studies of fibrogenesis conducted in many organs including the liver demonstrate that the primary source of the extracellular matrix in fibrosis is the myofibroblast. Hepatic myofibroblasts are not present in the normal liver but transdifferentiate from heterogeneous cell populations in response to a variety of fibrogenic stimuli. Debate still exists regarding the origin of hepatic myofibroblasts. It is considered that hepatic stellate cells and portal fibroblasts have fibrogenic potential and are the major origin of hepatic myofibroblasts. Depending on the primary site of injury the fibrosis may be present in the hepatic parenchyma as seen in chronic hepatitis or may be restricted to the portal areas as in most biliary diseases. It is suggested that hepatic injury of different etiology triggers the transdifferentiation to myofibroblasts from distinct cell populations. Here we discuss the origin and fate of myofibroblast in liver fibrosis.

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