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Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Mar 14, 2009; 15(10): 1194-1200
Published online Mar 14, 2009. doi: 10.3748/wjg.15.1194
Impact of asialoglycoprotein receptor deficiency on the development of liver injury
Serene ML Lee, Carol A Casey, Benita L McVicker
Serene ML Lee, Departments of Internal Medicine and Biochemistry & Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68105, United States
Carol A Casey, Benita L McVicker, 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
Author contributions: All authors contributed to the writing of this manuscript.
Correspondence to: Carol A Casey, PhD, Veterans Affairs Medical Center, Research Service (151), 4101 Woolworth Avenue, Omaha, NE 68105, United States.
Telephone: +1-402-9953737
Fax: +1-402-4490604
Received: December 17, 2008
Revised: January 6, 2009
Accepted: January 13, 2009
Published online: March 14, 2009

The asialoglycoprotein (ASGP) receptor is a well-characterized 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 mis-sorting 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 (CCl4) 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 toxin-mediated liver diseases.

Keywords: Asialoglycoprotein receptor, Asialoglycoprotein receptor deficient mice, Receptor-mediated endocytosis, Alcohol, Carbon tetrachloride, Anti-Fas, Lipopolysaccharide/galactosamine, Toxicant-induced liver injury