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Semin Liver Dis 2007; 27(4): 327-338
DOI: 10.1055/s-2007-991510
© Thieme Medical Publishers

Death Receptor-Mediated Liver Injury

Yuko Akazawa1 , Gregory J. Gores1
  • 1Division of Gastroenterology and Hepatology, Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota
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Publikationsverlauf

Publikationsdatum:
02. November 2007 (online)

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ABSTRACT

Apoptosis is a cardinal feature of liver injury. Death receptors are major mediators of the apoptotic pathway in the liver and have been implicated in the pathogenesis of diverse human diseases. More importantly, several studies have demonstrated a link between apoptosis and hepatic fibrosis; the latter is the most ominous consequence of chronic liver injury. In this article, we focus on the four death receptors: Fas, tumor necrosis factor receptor 1, tumor necrosis factor-related apoptosis-inducing ligand receptor 1, and tumor necrosis factor-related apoptosis-inducing ligand receptor 2. Although the death receptors have similar structures, they also possess distinct characteristics in their signaling pathways. Fas is abundantly expressed by all cells in the liver and plays a central role in variety of liver diseases. Tumor necrosis factor receptor 1 can induce both proapoptotic and prosurvival pathways. Tumor necrosis factor-related apoptosis-inducing ligand receptors likely trigger selective cell death in malignant and viral infected cells. Understanding the mechanism of liver injury caused by death receptors will enable therapeutic strategies to ameliorate human liver diseases.

KEYWORDS

Caspase inhibition - fibrosis - lipoapotosis

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Gregory J GoresM.D. F.A.C.P. 

Division of Gastroenterology and Hepatology, Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic College of Medicine

200 First Street SW, Rochester, MN 55905

eMail: gores.gregory@mayo.edu

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