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Significance of increased expression of decoy receptor 3 in chronic liver disease.

TitleSignificance of increased expression of decoy receptor 3 in chronic liver disease.
Publication TypeJournal Article
Year of Publication2009
AuthorsKim, S., Kotoula V., Hytiroglou P., Zardavas D., & Zhang L.
JournalDig Liver Dis
Volume41
Issue8
Pagination591-8
Date Published2009 Aug
ISSN1878-3562
KeywordsAdult, Aged, Apoptosis, Bile Ducts, Intrahepatic, Cell Line, Cell Line, Tumor, Cell Proliferation, Chronic Disease, Enzyme-Linked Immunosorbent Assay, Female, Hepatitis C, Chronic, Humans, Immunohistochemistry, In Situ Hybridization, Liver, Liver Cirrhosis, Liver Neoplasms, Liver Regeneration, Lymphocytes, Male, MAP Kinase Signaling System, Middle Aged, Receptors, Tumor Necrosis Factor, Member 6b
Abstract

BACKGROUND/AIMS: Considerable evidence has indicated that apoptosis plays an important role in hepatocyte death in chronic liver disease. However, the cellular and molecular mechanisms underlying liver regeneration in these diseases are largely unknown. Plausibly, certain molecules expressed to counteract apoptosis might provide survival advantage of certain liver cells. Therefore, we investigated a possible expression of decoy receptor 3 of the tumour necrosis factor receptor family in chronic liver diseases since decoy receptor 3 is known to inhibit apoptosis mediated by pro-apoptotic tumour necrosis factor family ligands including Fas ligand.METHODS: A series of liver biopsies from patients with different stages of fibrosis were subjected to immunohistochemistry and in situ hybridization.RESULTS: Both decoy receptor 3 protein and mRNA were mainly expressed in biliary epithelial cells and infiltrating lymphocytes in the diseased livers. Most noticeably, intense decoy receptor 3 expression was observed in newly developing biliary ductules in regenerative nodules as well as dysplastic nodules of cirrhotic livers. In addition, decoy receptor 3 secretion in hepatocellular carcinoma cells in culture was via the activation of mitogen-activated protein kinases.CONCLUSION: Decoy receptor 3 was specifically expressed in chronic liver diseases and hepatocellular carcinoma cells, and decoy receptor 3 might facilitate the survival of liver cells by exerting its anti-apoptotic activity during the progression of liver cirrhosis and hepatocarcinogenesis.

DOI10.1016/j.dld.2008.11.019
Alternate JournalDig Liver Dis
PubMed ID19195939
PubMed Central IDPMC3305787
Grant ListDK07643 / DK / NIDDK NIH HHS / United States
R43 DK076430-01 / DK / NIDDK NIH HHS / United States

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