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J Med Virol. 2004 Jan;72(1):52-9.

Hepatitis C virus core protein upregulates transforming growth factor-beta 1 transcription.

Author information

1
Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Abstract

The majority of persons with chronic hepatitis C virus (HCV) infection develop liver fibrosis. Transforming growth factor (TGF)-beta 1 plays a pivotal role in the pathogenesis of post-inflammatory liver scarring. To clarify the influence of HCV infection on liver fibrosis, a reporter assay was used to investigate the effect of viral proteins on TGF-beta 1 expression in human hepatoma cells. Of all HCV proteins investigated (core, E1/E2/p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B), only the core protein activated the TGF-beta 1 promoter and upregulated TGF-beta 1 expression measured by an RNase protection assay. Bases -376 to -331 bp in the promoter region of TGF-beta 1 are responsible for upregulation by HCV core protein, and the nuclear protein that binds to this region increased with the stimulation of HCV core protein. Blocking the mitogen-activated protein kinase pathway prevented upregulation of TGF-beta 1 by HCV core protein. The immunological response is supposed to be a major factor to cause the secretion of TGF-beta 1 from non-parenchymal cells, but the results suggest that the HCV core protein expression may upregulate directly TGF-beta 1 transcription in parenchymal cells and suggest a new paradigm for exacerbation of liver fibrosis by HCV infection.

PMID:
14635011
DOI:
10.1002/jmv.10545
[Indexed for MEDLINE]

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