Document Detail


Apoptosis as a mechanism for liver disease progression.
MedLine Citation:
PMID:  20960379     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Maria Eugenia Guicciardi; Gregory J Gores
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2010-10-19
Journal Detail:
Title:  Seminars in liver disease     Volume:  30     ISSN:  1098-8971     ISO Abbreviation:  Semin. Liver Dis.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-20     Completed Date:  2011-01-27     Revised Date:  2011-07-28    
Medline Journal Info:
Nlm Unique ID:  8110297     Medline TA:  Semin Liver Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  402-10     Citation Subset:  IM    
Copyright Information:
© Thieme Medical Publishers.
Affiliation:
College of Medicine, Mayo Clinic, Rochester, MN, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / physiology*
Caspases / physiology
DNA Damage / physiology
Disease Progression
Genes, bcl-2 / physiology
Hepatic Stellate Cells / physiology
Hepatocytes / physiology
Humans
Liver Diseases / physiopathology*
Phagocytosis / physiology
Toll-Like Receptor 9 / physiology
Grant Support
ID/Acronym/Agency:
DK 63947/DK/NIDDK NIH HHS; DK41876/DK/NIDDK NIH HHS; R01 DK041876-23/DK/NIDDK NIH HHS; R01 DK063947-09/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Toll-Like Receptor 9; EC 3.4.22.-/Caspases
Comments/Corrections

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