Apoptosis as a mechanism for liver disease progression

Maria Eugenia Guicciardi, Gregory James Gores

Research output: Contribution to journalArticle

113 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)402-410
Number of pages9
JournalSeminars in Liver Disease
Volume30
Issue number4
DOIs
StatePublished - 2010

Fingerprint

Disease Progression
Liver Diseases
Apoptosis
Hepatocytes
Fibrosis
Liver
Wounds and Injuries
Toll-Like Receptor 9
Death Domain Receptors
Nucleotide Motifs
Caspase Inhibitors
Phagocytes
Information Systems
Liver Cirrhosis
Cell Death
Ligands
Extracellular Vesicles
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Hepatology

Cite this

Apoptosis as a mechanism for liver disease progression. / Guicciardi, Maria Eugenia; Gores, Gregory James.

In: Seminars in Liver Disease, Vol. 30, No. 4, 2010, p. 402-410.

Research output: Contribution to journalArticle

Guicciardi, Maria Eugenia ; Gores, Gregory James. / Apoptosis as a mechanism for liver disease progression. In: Seminars in Liver Disease. 2010 ; Vol. 30, No. 4. pp. 402-410.
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