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

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Title
Regulation of transforming growth factor-β1 expression by the hepatitis B virus(HBV) X transactivator : role in HBV pathogenesis
Author(s)
Young Do Yoo; H Ueda; Keunchil Park; K C Flanders; Young Ik Lee; G Jay; Seong-Jin Kim
Bibliographic Citation
Journal of Clinical Investigation, vol. 97, no. 2, pp. 388-395
Publication Year
1996
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.
Keyword
hepatocellular carcinomaimmunohistochemistryTGF-β1transcriptionhepatitis B virus
ISSN
0021-9738
Publisher
Amer Soc Clinical Investigation Inc
DOI
http://dx.doi.org/10.1172/JCI118427
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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