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Activation of fibronectin gene expression by hepatitis B virus x antigen
Journal article   Open access   Peer reviewed

Activation of fibronectin gene expression by hepatitis B virus x antigen

P A Norton, H M G P V Reis, S Prince, J Larkin, J Pan, J Liu, Q Gong, M Zhu and M A Feitelson
Journal of viral hepatitis, v 11(4), pp 332-341
Jul 2004
DOI: https://doi.org/10.1111/j.1365-2893.2004.00555.x
PMID: 15230856
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1111/j.1365-2893.2004.00555.xView
Published, Version of Record (VoR) Open

Abstract

Immunohistochemistry Cell Line Liver - pathology RNA, Messenger - isolation & purification Tumor Suppressor Protein p53 - antagonists & inhibitors Hepatitis B virus - pathogenicity Humans Gene Expression Regulation RNA, Messenger - analysis NF-kappa B - metabolism Signal Transduction - genetics Fibronectins - metabolism Hepatitis B, Chronic - virology In Situ Hybridization Hepatitis B, Chronic - physiopathology Signal Transduction - physiology Trans-Activators - metabolism Fibronectins - genetics
The development of fibrosis and cirrhosis during chronic hepatitis B virus (HBV) infection correlates with the persistent expression of HBV x antigen (HBxAg), which acts in part, by stimulating selected signal transduction pathways, including nuclear factor kappa B (NF-kappa B). To identify NF-kappa B responsive genes that are differentially expressed in HBxAg-positive cells, HepG2 cells were stably transfected with HBxAg, and then with pZeoSV2 or pZeoSV2-I kappa B alpha. When RNAs from each culture were compared by PCR-select cDNA subtraction, fibronectin (FN) mRNA was shown to be strongly down-regulated by I kappa B alpha. Up-regulated expression of FN and co-expression between FN and HBxAg were observed in liver sections from HBV carriers that were stained for HBxAg and analysed for FN mRNA by in situ hybridization (ISH). In liver cell cultures, HBxAg increased the levels of FN mRNA and protein. This was because of the HBxAg-mediated trans-activation of the FN promoter, which was NF-kappa B-dependent. HBxAg also antagonized the repression of the FN promoter by the tumour suppressor, p53. Hence, the FN gene may be a natural target for HBxAg trans-activation, perhaps through activation of NF-kappa B and inactivation of p53, thereby contributing to the accumulation of FN in the liver over the course of chronic HBV infection.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Gastroenterology & Hepatology
Infectious Diseases
Virology
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