標題: Hepatitis B virus X antigen and aflatoxin B1 synergistically cause hepatitis, steatosis and liver hyperplasia in transgenic zebrafish
作者: Lu, Jeng-Wei
Yang, Wan-Yu
Lin, Yueh-Min
Jin, Shiow-Lian Catherine
Yuh, Chiou-Hwa
生物科技學系
Department of Biological Science and Technology
關鍵字: Hepatitis B virus X antigen;Aflatoxin B1;Liver diseases;Hyperplasia;Transgenic zebrafish
公開日期: 2013
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 immuno-staining. 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 5.75 months. (C) 2013 Elsevier GmbH. All rights reserved.
URI: http://hdl.handle.net/11536/22903
http://dx.doi.org/10.1016/j.acthis.2013.02.012
ISSN: 0065-1281
DOI: 10.1016/j.acthis.2013.02.012
期刊: ACTA HISTOCHEMICA
Volume: 115
Issue: 7
起始頁: 728
結束頁: 739
顯示於類別:期刊論文


文件中的檔案:

  1. 000325906600011.pdf