Regulation of transforming growth factor-beta 1 expression by the hepatitis B virus (HBV) X transactivator. Role in HBV pathogenesis.
Regulation of transforming growth factor-beta 1 expression by the hepatitis B virus (HBV) X transactivator. Role in HBV pathogenesis.
复制标题
DOI：
10.1172/jci118427
复制
发表时间：
1996-01
期刊：
影响因子：
--
通讯作者：
Y. Yoo;H. Ueda;K. Park;K. Flanders;Y. I. Lee;G. Jay;Seong-Jin Kim
中科院分区：
文献类型：
--
作者：
Y. Yoo;H. Ueda;K. Park;K. Flanders;Y. I. Lee;G. Jay;Seong-Jin Kim
TGF-β 1与肝脏疾病的发病机制有关。慢性肝炎、肝硬化和肝癌患者肝细胞中B型肝炎病毒X（HBx）抗原的高检出率表明HBx和TGF-β 1的表达可能相关。为了测试这种可能性，我们检测了表达HBx基因的转基因小鼠肝脏中TGF-β 1的表达。我们表明，TGF-β 1和Hbx蛋白的表达模式是相似的，在这些小鼠和HBx激活TGF-β 1基因在转染的肝癌细胞的转录。TGF-β 1基因内的顺式作用元件是Egr家族转录因子的结合位点，该元件对Hbx的调节起反应。我们进一步表明，Egr-1蛋白与HBx蛋白，使HBx参与转录调控的立即早期基因。我们的研究结果表明，Hbx的表达可能会诱导TGF-β 1的表达在感染的早期阶段，并提高TGF-β 1可能在B型肝炎病毒的发病机制中发挥作用的可能性。
TGF-beta 1 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-beta 1 may be associated. To test this possibility, we examined the expression of TGF-beta 1 in the liver of transgenic mice expressing the HBx gene. We show that the patterns of expression of TGF-beta 1 and Hbx protein are similar in these mice and that HBx activates transcription of the TGF-beta 1 gene in transfected hepatoma cells. The cis-acting element within the TGF-beta 1 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-beta 1 in the early stages of infection and raise the possibility that TGF-beta 1 may play a role in hepatitis B virus pathogenesis.