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Impact of asialoglycoprotein receptor deficiency on the development of liver injury

World Journal of Gastroenterology 2009年第10期15卷 1194-1200页

作者： Serene ML Lee Carol A Casey Benita L McVicker Departments of Internal Medicine and Biochemistry & Molecular Biology University of Nebraska Medical Center Omaha NE 68105 United States Liver Study Unit Department of Veterans Affairs Medical Center and Departments of Internal Medicine and Biochemistry & Molecular Biology University of Nebraska Medical Center Omaha NE 68105 United States

The asialoglycoprotein （ASGP） receptor is a wellcharacterized hepatic receptor that is recycled via the common cellular process of receptor-mediated endocytosis （RME）. The RME process plays an integral part in the proper trafficking and routing of receptors and ligands in the healthy cell. Thus, the missorting or altered transport of proteins during RME is thought to play a role in several diseases associated with hepatocyte and liver dysfunction. Previously, we examined in detail alterations that occur in hepatocellular RME and associated receptor functions as a result of one particular liver injury, alcoholic liver disease （ALD）. The studies revealed profound ethanol- mediated impairments to the ASGP receptor and the RME process, indicating the importance of this receptor and the maintenance of proper endocytic events in normal tissue. To further clarify these observations, studies were performed utilizing knockout mice （lacking a functional ASGP receptor） to which were administered several liver toxicants. In addition to alcohol, we examined the effects following administration of anti- Fas （CD95） antibody, carbon tetrachloride （CCh） and lipopolysaccharide （LPS）/galactosamine. The results of these studies demonstrated that the knockout mice sustained enhanced liver injury in response to all of the treatments, as shown by increased indices of liver damage, such as enhancement of serum enzyme levels, histopathological scores, as well as hepatocellular death. Overall, the work completed to date suggests a possible link between hepatic receptors and liver injury. In particular, adequate function and content of the ASGP receptor may provide protection against various toxinmediated liver diseases.

关键词： Asialoglycoprotein receptor asialoglycoproteinreceptor deficient mice Receptor-mediatedendocytosis Alcohol Carbon tetrachloride Anti-Fas Lipopolysaccharide/galactosamine Toxicant-induced liverinjury

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