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International Journal of Molecular Medicine
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Print ISSN: 1107-3756 Online ISSN: 1791-244X
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August-2016 Volume 38 Issue 2

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Article

p-CREB-1 promotes hepatic fibrosis through the transactivation of transforming growth factor-β1 expression in rats

  • Authors:
    • Pei Wang
    • Liang Deng
    • Chunbo Zhuang
    • Chunwei Cheng
    • Keshu Xu
  • View Affiliations / Copyright

    Affiliations: Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
  • Pages: 521-528
    |
    Published online on: June 8, 2016
       https://doi.org/10.3892/ijmm.2016.2630
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Abstract

Phosphorylated cAMP-responsive element binding protein-1 (p-CREB-1) is an important transcription factor which has been reported to be implicated in fibrogenesis. However, the association between p-CREB-1 and transforming growth factor-β1 (TGF-β1)-mediated liver fibrogenesis remains poorly understood. In the present study, exogenous TGF-β1 recombinant protein was used to activate hepatic stellate cells (HSCs), and we established a rat model of tetrachloromethane (CCl4)‑induced liver fibrosis. Loss- and gain-of-function studies were performed to examine the role of p-CREB-1 in liver fibrogenesis, and the detailed mechanism responsible for these effects was further explored using chromatin immunoprecipitation and luciferase reporter gene assays. We found that p-CREB-1 expression was significantly upregulated in a rat model of hepatic fibrosis. We also demonstrated that p-CREB-1 increased TGF-β1 expression and auto‑induction in HSCs, through directly binding to the CRE site within the TGF-β1 promoter in order to enhance its transcriptional activity. Moreover, lentivirus-mediated CREB-1 overexpression promoted hepatic fibrogenesis in rats. These findings suggest that p-CREB-1 may function as a potent profibrogenic factor through the transactivation of TGF-β1 expression in liver fibrosis.
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Copy and paste a formatted citation
Spandidos Publications style
Wang P, Deng L, Zhuang C, Cheng C and Xu K: p-CREB-1 promotes hepatic fibrosis through the transactivation of transforming growth factor-β1 expression in rats. Int J Mol Med 38: 521-528, 2016.
APA
Wang, P., Deng, L., Zhuang, C., Cheng, C., & Xu, K. (2016). p-CREB-1 promotes hepatic fibrosis through the transactivation of transforming growth factor-β1 expression in rats. International Journal of Molecular Medicine, 38, 521-528. https://doi.org/10.3892/ijmm.2016.2630
MLA
Wang, P., Deng, L., Zhuang, C., Cheng, C., Xu, K."p-CREB-1 promotes hepatic fibrosis through the transactivation of transforming growth factor-β1 expression in rats". International Journal of Molecular Medicine 38.2 (2016): 521-528.
Chicago
Wang, P., Deng, L., Zhuang, C., Cheng, C., Xu, K."p-CREB-1 promotes hepatic fibrosis through the transactivation of transforming growth factor-β1 expression in rats". International Journal of Molecular Medicine 38, no. 2 (2016): 521-528. https://doi.org/10.3892/ijmm.2016.2630
Copy and paste a formatted citation
x
Spandidos Publications style
Wang P, Deng L, Zhuang C, Cheng C and Xu K: p-CREB-1 promotes hepatic fibrosis through the transactivation of transforming growth factor-β1 expression in rats. Int J Mol Med 38: 521-528, 2016.
APA
Wang, P., Deng, L., Zhuang, C., Cheng, C., & Xu, K. (2016). p-CREB-1 promotes hepatic fibrosis through the transactivation of transforming growth factor-β1 expression in rats. International Journal of Molecular Medicine, 38, 521-528. https://doi.org/10.3892/ijmm.2016.2630
MLA
Wang, P., Deng, L., Zhuang, C., Cheng, C., Xu, K."p-CREB-1 promotes hepatic fibrosis through the transactivation of transforming growth factor-β1 expression in rats". International Journal of Molecular Medicine 38.2 (2016): 521-528.
Chicago
Wang, P., Deng, L., Zhuang, C., Cheng, C., Xu, K."p-CREB-1 promotes hepatic fibrosis through the transactivation of transforming growth factor-β1 expression in rats". International Journal of Molecular Medicine 38, no. 2 (2016): 521-528. https://doi.org/10.3892/ijmm.2016.2630
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