Journal of Cellular Biochemistry

Wnt antagonist SFRP3 inhibits the differentiation of mouse hepatic progenitor cells

Authors

  • Yang Bi,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Jiayi Huang,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Yun He,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Gao-Hui Zhu,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Yuxi Su,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Bai-Cheng He,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Jinyong Luo,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Yi Wang,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Quan Kang,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Qing Luo,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Liang Chen,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Guo-Wei Zuo,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Wei Jiang,

    1. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Bo Liu,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Qiong Shi,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Min Tang,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Bing-Qiang Zhang,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Yaguang Weng,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
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  • Ailong Huang,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
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  • Lan Zhou,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Tao Feng,

    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Hue H. Luu,

    1. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Rex C. Haydon,

    1. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
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  • Tong-Chuan He,

    Corresponding author
    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
    • Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, 5841 South Maryland Avenue, MC3079, Chicago, IL 60637.
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  • Ni Tang

    Corresponding author
    1. Key Laboratory of Diagnostic Medicine designated by the Ministry of Education of China, and the Affiliated Hospitals of Chongqing Medical University, Chongqing, China
    2. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, Chicago, Illinois
    • The Institute for Viral Hepatitis Research, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
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  • The authors declare no financial interests.

  • Yang Bi and Jiayi Huang contributed equally to the work.

Abstract

Wnt/β-catenin pathway plays an important role in regulating embryonic development. Hepatocytes differentiate from endoderm during development. Hepatic progenitor cells (HPCs) have been isolated from fetal liver and extrahepatic tissues. Most current studies in liver development and hepatic differentiation have been focused on Wnts, β-catenin, and their receptors. Here, we sought to determine the role of Wnt antagonists in regulating hepatic differentiation of fetal liver-derived HPCs. Using mouse liver tissues derived from embryonic day E12.5 to postnatal day (PD) 28, we found that 13 of the 19 Wnt genes and almost all of Wnt receptors/co-receptors were expressed in most stages. However, Wnt antagonists SFRP2, SFRP3, and Dkk2 were only detected in the early stages. We established and characterized the reversible stable HPCs derived from E14.5 mouse fetal liver (HP14.5). HP14.5 cells were shown to express high levels of early liver progenitor cell markers, but low levels or none of late liver markers. HP14.5 cells were shown to differentiate into mature hepatocytes upon dexamethasone (Dex) stimulation. Dex-induced late marker expression and albumin promoter activity in HP14.5 cells were inhibited by exogenous expression of SFRP3. Furthermore, Dex-induced glycogen synthesis of PAS-positive HP14.5 cells was significantly inhibited by SFRP3. Therefore, our results have demonstrated that the expression of Wnt antagonists decreases as hepatic differentiation progresses, suggesting that a balanced Wnt signaling may be critical during mouse liver development and hepatic differentiation. J. Cell. Biochem. 108: 295–303, 2009. © 2009 Wiley-Liss, Inc.

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