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Geranylgeranylacetone decreases the production of hepatitis B virus‐related antigen by comprehensive downregulation of mRNA transcription activity
Author(s) -
Haraguchi Masafumi,
Miuma Satoshi,
Yamamoto Kazuo,
Nakao Yasuhiko,
Ichikawa Tatsuki,
Kanda Yasuko,
Sasaki Ryu,
Fukushima Masanori,
Akazawa Yuko,
Miyaaki Hisamitsu,
Nakao Kazuhiko
Publication year - 2021
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.15394
Subject(s) - hepatitis b virus , cccdna , enhancer , microbiology and biotechnology , endoplasmic reticulum , virology , western blot , antigen , hepatocyte , downregulation and upregulation , promoter , biology , medicine , transcription factor , virus , gene expression , immunology , hbsag , in vitro , gene , biochemistry
Background and Aim Elimination of hepatitis B virus (HBV) is infrequently achieved with current therapies. Therefore, more effective anti‐HBV therapy is needed. We previously reported that geranylgeranylacetone (GGA) showed anti‐hepatitis C virus activity in human hepatoma cells. In this study, we examined the anti‐HBV activity of GGA. Methods We used HepG2.2.15.7 cells, PXB cells infected with HBV, Huh7 cells transfected with linear HBV, and PLC/PRF/5 cells as HBV‐infected hepatocyte models. After GGA treatment, HBV‐related antigen was measured by chemiluminescent immunoassay. HBV‐related mRNA was examined by Northern blot. cccDNA and endoplasmic reticulum stress markers were measured by real‐time polymerase chain reaction. The activities of HBV promoters and enhancer regions were examined using luciferase vectors. Results After GGA treatment, hepatitis B surface antigen and hepatitis B e antigen secretion was decreased in all HBV‐infected hepatocyte models. HBV‐related mRNA was also decreased by GGA treatment, although cccDNA levels were not affected. Additionally, the activity of HBV S1 and S2 promoter region and Enhancer 1/Enhancer 2/core promoter region was reduced by GGA treatment. The mRNA expression of the main transcription factors, hepatocyte nuclear factor 3 and 4 and CCAAT/enhancer binding protein, was also decreased. Further, the expression levels of endoplasmic reticulum stress markers were increased by GGA treatment, which reflected the change in HBV‐related antigen secretion. Conclusions Geranylgeranylacetone treatment reduces HBV‐related protein levels by suppressing comprehensive downregulation of HBV promoter and enhancer activity, which might be caused by decreased hepatic transcription factor expression. GGA treatment may enhance anti‐HBV effects in combination with other therapies.