Impact of asialoglycoprotein receptor deficiency on the development of liver injury

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Abstract

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 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 ethanolmediated 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.

Original languageEnglish (US)
Pages (from-to)1194-1200
Number of pages7
JournalWorld Journal of Gastroenterology
Volume15
Issue number10
DOIs
Publication statusPublished - Mar 14 2009

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Keywords

  • Alcohol
  • Anti-fas
  • Asialoglycoprotein receptor
  • Asialoglycoprotein receptor deficient mice
  • Carbon tetrachloride
  • Lipopolysaccharide/galactosamine
  • Receptor-mediated endocytosis
  • Toxicant-induced liver injury

ASJC Scopus subject areas

  • Gastroenterology

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