Hepatitis B virus X antigen and aflatoxin B1 synergistically cause hepatitis, steatosis and liver hyperplasia in transgenic zebrafish

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题名:	Hepatitis B virus X antigen and aflatoxin B1 synergistically cause hepatitis, steatosis and liver hyperplasia in transgenic zebrafish
作者:	金秀蓮;Lu, Jeng-Wei;Yang, Wan-Yu;Lin, Yueh-Min;Jin, Shiow-Lian Catherine;Yuh, Chiou-Hwa
贡献者:	生醫理工學院生命科學系
关键词:	Aflatoxin B1;Aflatoxin B1 - administration & dosage;animal models;Animals;Animals, Genetically Modified;carcinoma;Carcinoma, Hepatocellular - genetics;Carcinoma, Hepatocellular - metabolism;Carcinoma, Hepatocellular - pathology;Caspase 3 - genetics;Caspase 3 - metabolism;caspase-3;cell cycle;Cell Cycle Proteins - agonists;Cell Cycle Proteins - genetics;Cell Cycle Proteins - metabolism;Danio rerio;fatty liver;Fatty Liver - chemically induced;Fatty Liver - genetics;Fatty Liver - metabolism;Fatty Liver - pathology;fish;fluorescence;Freshwater;Gene Expression - drug effects;genes;glycogen;Glycogen - biosynthesis;hepatitis;Hepatitis B - genetics;Hepatitis B - metabolism;Hepatitis B - pathology;Hepatitis B virus;Hepatitis B virus X antigen;hepatoma;histopathology;Humans;Hyperplasia;Hyperplasia - genetics;Hyperplasia - metabolism;Hyperplasia - pathology;Immunohistochemistry;inflammation;Injections, Intraperitoneal;lipid metabolism;Lipid Metabolism - drug effects;liver;Liver - metabolism;Liver - pathology;Liver diseases;patients;Polymerase Chain Reaction;proliferating cell nuclear antigen;Proliferating Cell Nuclear Antigen - genetics;Proliferating Cell Nuclear Antigen - metabolism;protein synthesis;reverse transcriptase polymerase chain reaction;synergism;Trans-Activators - genetics;Trans-Activators - metabolism;transgenic animals;Transgenic zebrafish;Zebrafish
日期:	2013-09-01
上传时间:	2026-04-23 11:12:59 (UTC+8)
出版者:	Urban und Fischer Verlag Jena;Germany: Elsevier GmbH
摘要:	摘要： Aflatoxin B1 (AFB1) and the hepatitis B virus X antigen (HBx) are linked to the formation of liver diseases and hepatocellular carcinoma (HCC). The aim of this study was to investigate the synergistic effects between HBx and AFB1 in causing liver disorders using a transgenic zebrafish animal model. Histopathology, Periodic acid-Schiff (PAS) staining, Sirius red staining, TdT-mediated dUTP Nick End Labeling (TUNEL) assay, immunohistochemistry, and quantitative reverse transcriptase-polymerase chain reaction (Q-RT-PCR) were used to examine the livers of the HBx transgenic fish injected with AFB1. We found that HBx and AFB1 synergistically promoted steatosis as indicated by histopathological examinations and the increased expression of lipogenic factors, enzymes, and genes related to lipid metabolism. Moreover, treatment of AFB1 in HBx transgenic fish accelerated the development of liver hyperplasia and enhanced the expression of cell cycle related genes. PCNA was co-localized with active caspase 3 protein expression in HBx zebrafish liver samples and human HBV positive HCC samples by double fluorescence immunostaining. Finally, we found that in human patients with liver disease, significant glycogen accumulated in the inflammation, cirrhosis stage, and all cases of hepatocellular and cholangiocellular carcinoma showed a moderate cytoplasmic accumulation of glycogen. Our data demonstrated a synergistic effect of AFB1 and HBx on the regulation of lipid metabolism related genes and cell cycle/division-related genes which might contribute to enhanced steatosis and hyperplasia at 5.75months. 其他題名： Acta Histochem 出版者： Germany: Elsevier GmbH 出版日期： 2013-09 出處： Acta Histochemica, 2013-09, Vol.115 (7), p.728-739 版權： 2013 Elsevier GmbH 版權： Copyright © 2013 Elsevier GmbH. All rights reserved. 識別號： ISSN: 0065-1281 識別號： ISSN: 1618-0372 識別號： EISSN: 1618-0372 識別號： DOI: 10.1016/j.acthis.2013.02.012 識別號： PMID: 23499292
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