Regulation of transforming growth factor-β1 expression by the hepatitis B virus (HBV) X transactivator: Role in HBV pathogenesis

Young Do Yoo, Hiroyuki Ueda, Keunchil Park, Kathy C. Flanders, Young Ik Lee, Gilbert Jay, Seong Jin Kim

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146 Citations (Scopus)

Abstract

TGF-β1 has been implicated in the pathogenesis of liver disease. The high frequency of detection of the hepatitis B virus X (HBx) antigen in liver cells from patients with chronic hepatitis, cirrhosis, and liver cancer suggested that expression of HBx and TGF-β1 may be associated. To test this possibility, we examined the expression of TGF-β1 in the liver of transgenic mice expressing the HBx gene. We show that the patterns of expression of TGF-β1 and Hbx protein are similar in these mice and that HBx activates transcription of the TGF-β1 gene in transfected hepatoma cells. The cis-acting element within the TGF-β1 gene that is responsive to regulation by Hbx is the binding site for the Egr family of transcription factors. We further show that the Egr-1 protein associates with the HBx protein, allowing HBx to participate in the transcriptional regulation of immediate-early genes. Our results suggest that expression of Hbx might induce expression of TGF-β1 in the early stages of infection and raise the possibility that TGF-ßl may play a role in hepatitis B virus pathogenesis.

Original languageEnglish
Pages (from-to)388-395
Number of pages8
JournalJournal of Clinical Investigation
Volume97
Issue number2
Publication statusPublished - 1996 Jan 15
Externally publishedYes

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Keywords

  • Hepatitis B virus
  • Hepatocellular carcinoma
  • Immunohistochemistry
  • TGF-β1
  • Transcription

ASJC Scopus subject areas

  • Medicine(all)

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