RRC ID 1991
著者 Taniguchi H, Kato N, Otsuka M, Goto T, Yoshida H, Shiratori Y, Omata M.
タイトル Hepatitis C virus core protein upregulates transforming growth factor-beta 1 transcription.
ジャーナル J Med Virol
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.
巻・号 72(1)
ページ 52-9
公開日 2004-1-1
DOI 10.1002/jmv.10545
PMID 14635011
MeSH Hepacivirus / pathogenicity* Hepatitis C, Chronic / physiopathology* Hepatitis C, Chronic / virology Humans Liver Cirrhosis / physiopathology Liver Cirrhosis / virology Mitogen-Activated Protein Kinases / metabolism Promoter Regions, Genetic Transcription, Genetic Transforming Growth Factor beta / metabolism* Transforming Growth Factor beta1 Tumor Cells, Cultured Up-Regulation* Viral Core Proteins / metabolism* Viral Proteins / metabolism
IF 2.021
引用数 92
WOS 分野 VIROLOGY
リソース情報
ヒト・動物細胞 Hep G2