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.
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.
Authors: R M Pitti; S A Marsters; D A Lawrence; M Roy; F C Kischkel; P Dowd; A Huang; C J Donahue; S W Sherwood; D T Baldwin; P J Godowski; W I Wood; A L Gurney; K J Hillan; R L Cohen; A D Goddard; D Botstein; A Ashkenazi Journal: Nature Date: 1998-12-17 Impact factor: 49.962
Authors: M F Favata; K Y Horiuchi; E J Manos; A J Daulerio; D A Stradley; W S Feeser; D E Van Dyk; W J Pitts; R A Earl; F Hobbs; R A Copeland; R L Magolda; P A Scherle; J M Trzaskos Journal: J Biol Chem Date: 1998-07-17 Impact factor: 5.157
Authors: Giorgos Bamias; Michalis Gizis; Ioanna Delladetsima; Eyfrosyni Laoudi; Spyros I Siakavellas; Ioannis Koutsounas; Garyfallia Kaltsa; John Vlachogiannakos; Irene Vafiadis-Zouboulis; George L Daikos; George V Papatheodoridis; Spiros D Ladas Journal: Can J Gastroenterol Hepatol Date: 2016-08-09