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Smad6 Suppresses the Growth and Self-Renewal of Hepatic Progenitor Cells

Authors

  • Ze-Yang Ding,

    1. Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Hui-Fang Liang,

    1. Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Guan-Nan Jin,

    1. Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    2. Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Wei-Xun Chen,

    1. Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Wei Wang,

    1. Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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  • Pran K. Datta,

    1. Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
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  • Ming-Zhi Zhang,

    1. Department of Medicine and Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee
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  • Bixiang Zhang,

    Corresponding author
    1. Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    • Correspondence to:

      Dr. Bixiang Zhang, Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, 430030 Wuhan, China

      E-mail: bixiangzhang@163.com

      Correspondence to:

      Dr. Xiao-ping Chen, Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, 430030 Wuhan, China

      E-mail: chenxp@medmail.com.cn

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  • Xiao-Ping Chen

    Corresponding author
    1. Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
    • Correspondence to:

      Dr. Bixiang Zhang, Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, 430030 Wuhan, China

      E-mail: bixiangzhang@163.com

      Correspondence to:

      Dr. Xiao-ping Chen, Hepatic Surgery Centre, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, 430030 Wuhan, China

      E-mail: chenxp@medmail.com.cn

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  • Conflicts of interest: nothing to declare.
  • Ze-Yang Ding, Hui-Fang Liang, and Guan-Nan Jin contributed equally to this work.

Abstract

Activation of hepatic progenitor cells (HPCs) is commonly observed in chronic liver disease and Wnt/β-catenin signaling plays a crucial role in the expansion of HPCs. However, the molecular mechanisms that regulate the activation of Wnt/β-catenin signaling in the liver, especially in HPCs, remain largely elusive. Here, we reported that ectopic expression of Smad6 suppressed the proliferation and self-renewal of WB-F344 cells, a HPC cell line. Mechanistically, we found that Smad6 inhibited Wnt/β-catenin signaling through promoting the interaction of C-terminal binding protein (CtBP) with β-catenin/T-cell factor (TCF) complex to inhibit β-catenin mediated transcriptional activation in WB-F344 cells. We used siRNA targeting β-catenin to demonstrate that Wnt/β-catenin signaling was required for the proliferation and self-renewal of HPCs. Taken together, these results suggest that Smad6 is a regulatory molecule which regulates the proliferation, self-renewal and Wnt/β-catenin signaling in HPCs. J. Cell. Physiol. 229: 651–660, 2014. © 2013 Wiley Periodicals, Inc.

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