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

Wang,Pei; Deng,Liang; Zhuang,Chunbo; Cheng,Chunwei; Xu,Keshu

doi:10.3892/ijmm.2016.2630

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
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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
Published online on: June 8, 2016 https://doi.org/10.3892/ijmm.2016.2630
Pages: 521-528

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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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