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Semin Liver Dis 2010; 30(4): 402-410
DOI: 10.1055/s-0030-1267540
© Thieme Medical Publishers

Apoptosis as a Mechanism for Liver Disease Progression

Maria Eugenia Guicciardi1 , Gregory J. Gores1
  • 1Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, Rochester, Minnesota
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Publication History

Publication Date:
19 October 2010 (online)

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ABSTRACT

Hepatocyte injury is ubiquitous in clinical practice, and the mode of cell death associated with this injury is often apoptosis, especially by death receptors. Information from experimental systems demonstrates that hepatocyte apoptosis is sufficient to cause liver hepatic fibrogenesis. The mechanisms linking hepatocyte apoptosis to hepatic fibrosis remain incompletely understood, but likely relate to engulfment of apoptotic bodies by professional phagocytic cells and stellate cells, and release of mediators by cells undergoing apoptosis. Inhibition of apoptosis with caspase inhibitors has demonstrated beneficial effects in murine models of hepatic fibrosis. Recent studies implicating Toll-like receptor 9 in liver injury and fibrosis are also of particular interest. Engulfment of apoptotic bodies is one mechanism by which the TLR9 ligand (CpG DNA motifs) could be delivered to this intracellular receptor. These concepts suggest therapy focused on interrupting the cellular mechanisms linking apoptosis to fibrosis would be useful in human liver diseases.

KEYWORDS

Bcl-2 proteins - caspase inhibitors - death receptors - stellate cells - Toll-like receptor 9

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Gregory J GoresM.D. 

Reuben R. Eisenberg Professor of Medicine and Chair, Division of Gastroenterology and Hepatology

College of Medicine, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905

Email: gores.gregory@mayo.edu