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This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/G357    most recent 00456.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Siegmund, S. V. Articles by Schwabe, R. F. Search for Related Content PubMed PubMed Citation Articles by Siegmund, S. V. Articles by Schwabe, R. F.

THEMES

Endocannabinoids and Liver Disease. II. Endocannabinoids in the pathogenesis and treatment of liver fibrosis

¹Department of Medicine II, University Hospital Mannheim, University of Heidelberg, Mannheim, Germany; and ²Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, New York

Submitted 4 October 2007 ; accepted in final form 15 November 2007

Hepatic fibrosis is the response of the liver to chronic injury and is associated with portal hypertension, progression to hepatic cirrhosis, liver failure, and high incidence of hepatocellular carcinoma. On a molecular level, a large number of signaling pathways have been shown to contribute to the activation of fibrogenic cell types and the subsequent accumulation of extracellular matrix in the liver. Recent evidence suggests that the endocannabinoid system is an important part of this complex signaling network. In the injured liver, the endocannabinoid system is upregulated both at the level of endocannabinoids and at the endocannabinoid receptors CB1 and CB2. The hepatic endocannabinoid system mediates both pro- and antifibrogenic effects by activating distinct signaling pathways that differentially affect proliferation and death of fibrogenic cell types. Here we will summarize current findings on the role of the hepatic endocannabinoid system in liver fibrosis and discuss emerging options for its therapeutic exploitation.

hepatic stellate cell; cell death; anandamide; 2-arachidonoyl glycerol

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