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Article

Post‑translational modification of CREB‑1 decreases collagen I expression by inhibiting the TGF‑β1 signaling pathway in rat hepatic stellate cells

  • Authors:
    • Xiaoling Deng
    • Liang Deng
    • Pei Wang
    • 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 630014, P.R. China
  • Pages: 5751-5759
    |
    Published online on: November 7, 2016
       https://doi.org/10.3892/mmr.2016.5926
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Abstract

Liver fibrosis is a reversible wound‑healing response to liver damage. Following liver injury, activated hepatic stellate cells (HSCs) cause excessive deposition of collagen and other components of the extracellular matrix, which may eventually impair liver function. Transforming growth factor‑β1 (TGF‑β1) is critical for the development of liver fibrosis, and acts by activating HSCs, stimulating matrix deposition and inducing other profibrotic responses. Certain studies have demonstrated that the transcription factor, cyclic adenosine monophosphate (cAMP)‑response element binding protein‑1 (CREB‑1) is important in the inhibition of fibrosis; however, the underlying mechanism remains to be elucidated. The present study hypothesized that CREB‑1 inhibits fibrosis via blocking the TGF‑β1 signaling pathway in HSCs. Treatment with the cAMP‑elevating agent, forskolin stimulated CREB‑1 phosphorylation and transcription activation in HSCs. In addition, treatment with the histone deacetylase inhibitor, trichostatin A extended CREB‑1 phosphorylation. The present study used a pRSV‑CREB‑1 expression vector to upregulate CREB‑1 gene expression. The results indicated that activated CREB‑1 reduced TGF‑β1‑stimulated expression of collagen I, activated Smad2/3 and upregulated expression of Smad7. In addition, activated CREB‑1 attenuated the activation of extracellular signal‑regulated kinase 1/2 induced by TGF‑β1, expression of Ras homolog gene family, member A (RhoA) and Rho‑associated coiled‑coil containing protein kinase 1. Thus, post‑translational modification of CREB‑1 inhibited the profibrotic effects of TGF‑β1 in HSCs via Smad‑dependent and ‑independent signaling pathways.
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Copy and paste a formatted citation
Spandidos Publications style
Deng X, Deng L, Wang P, Cheng C and Xu K: Post‑translational modification of CREB‑1 decreases collagen I expression by inhibiting the TGF‑β1 signaling pathway in rat hepatic stellate cells. Mol Med Rep 14: 5751-5759, 2016.
APA
Deng, X., Deng, L., Wang, P., Cheng, C., & Xu, K. (2016). Post‑translational modification of CREB‑1 decreases collagen I expression by inhibiting the TGF‑β1 signaling pathway in rat hepatic stellate cells. Molecular Medicine Reports, 14, 5751-5759. https://doi.org/10.3892/mmr.2016.5926
MLA
Deng, X., Deng, L., Wang, P., Cheng, C., Xu, K."Post‑translational modification of CREB‑1 decreases collagen I expression by inhibiting the TGF‑β1 signaling pathway in rat hepatic stellate cells". Molecular Medicine Reports 14.6 (2016): 5751-5759.
Chicago
Deng, X., Deng, L., Wang, P., Cheng, C., Xu, K."Post‑translational modification of CREB‑1 decreases collagen I expression by inhibiting the TGF‑β1 signaling pathway in rat hepatic stellate cells". Molecular Medicine Reports 14, no. 6 (2016): 5751-5759. https://doi.org/10.3892/mmr.2016.5926
Copy and paste a formatted citation
x
Spandidos Publications style
Deng X, Deng L, Wang P, Cheng C and Xu K: Post‑translational modification of CREB‑1 decreases collagen I expression by inhibiting the TGF‑β1 signaling pathway in rat hepatic stellate cells. Mol Med Rep 14: 5751-5759, 2016.
APA
Deng, X., Deng, L., Wang, P., Cheng, C., & Xu, K. (2016). Post‑translational modification of CREB‑1 decreases collagen I expression by inhibiting the TGF‑β1 signaling pathway in rat hepatic stellate cells. Molecular Medicine Reports, 14, 5751-5759. https://doi.org/10.3892/mmr.2016.5926
MLA
Deng, X., Deng, L., Wang, P., Cheng, C., Xu, K."Post‑translational modification of CREB‑1 decreases collagen I expression by inhibiting the TGF‑β1 signaling pathway in rat hepatic stellate cells". Molecular Medicine Reports 14.6 (2016): 5751-5759.
Chicago
Deng, X., Deng, L., Wang, P., Cheng, C., Xu, K."Post‑translational modification of CREB‑1 decreases collagen I expression by inhibiting the TGF‑β1 signaling pathway in rat hepatic stellate cells". Molecular Medicine Reports 14, no. 6 (2016): 5751-5759. https://doi.org/10.3892/mmr.2016.5926
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