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

Research output: Contribution to journalArticle

145 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

Fingerprint

Trans-Activators
Transforming Growth Factors
Hepatitis B virus
Murine hepatitis virus
Genes
Immediate-Early Genes
Liver
Chronic Hepatitis
Liver Neoplasms
Transgenic Mice
Liver Diseases
Hepatocellular Carcinoma
Proteins
Fibrosis
Transcription Factors
Binding Sites
Infection

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Regulation of transforming growth factor-β1 expression by the hepatitis B virus (HBV) X transactivator : Role in HBV pathogenesis. / Yoo, Young Do; Ueda, Hiroyuki; Park, Keunchil; Flanders, Kathy C.; Lee, Young Ik; Jay, Gilbert; Kim, Seong Jin.

In: Journal of Clinical Investigation, Vol. 97, No. 2, 15.01.1996, p. 388-395.

Research output: Contribution to journalArticle

Yoo, Young Do ; Ueda, Hiroyuki ; Park, Keunchil ; Flanders, Kathy C. ; Lee, Young Ik ; Jay, Gilbert ; Kim, Seong Jin. / Regulation of transforming growth factor-β1 expression by the hepatitis B virus (HBV) X transactivator : Role in HBV pathogenesis. In: Journal of Clinical Investigation. 1996 ; Vol. 97, No. 2. pp. 388-395.
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