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Tcf3 promotes cell migration and wound repair through regulation of lipocalin 2

Author

Listed:
  • Qi Miao

    (Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505)

  • Amy T. Ku

    (Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505
    Baylor College of Medicine, One Baylor Plaza, BCM 505)

  • Yudai Nishino

    (Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505)

  • Jeffrey M. Howard

    (Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505
    Baylor College of Medicine, One Baylor Plaza, BCM 505
    Medical Scientist Training Program, Baylor College of Medicine, One Baylor Plaza, BCM 505)

  • Ajay S. Rao

    (Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505)

  • Timothy M. Shaver

    (Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505)

  • Gloria E. Garcia

    (Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505)

  • Diep N. Le

    (Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505)

  • Kristen L. Karlin

    (Baylor College of Medicine, One Baylor Plaza, BCM 505
    Baylor College of Medicine, Baylor Plaza, BCM 505)

  • Thomas F. Westbrook

    (Baylor College of Medicine, One Baylor Plaza, BCM 505
    Baylor College of Medicine, Baylor Plaza, BCM 505
    Baylor College of Medicine, One Baylor Plaza, BCM 505
    Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, BCM 505)

  • Valeria Poli

    (Molecular Biotechnology Center, University of Turin, Via Nizza 52)

  • Hoang Nguyen

    (Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, One Baylor Plaza, BCM 505
    Baylor College of Medicine, One Baylor Plaza, BCM 505
    Dan L. Duncan Cancer Center, Baylor College of Medicine, One Baylor Plaza, BCM 505
    Baylor College of Medicine, One Baylor Plaza, BCM 505)

Abstract

Cell migration is an integral part of re-epithelialization during skin wound healing, a complex process involving molecular controls that are still largely unknown. Here we identify a novel role for Tcf3, an essential transcription factor regulating embryonic and adult skin stem cell functions, as a key effector of epidermal wound repair. We show that Tcf3 is upregulated in skin wounds and that Tcf3 overexpression accelerates keratinocyte migration and skin wound healing. We also identify Stat3 as an upstream regulator of Tcf3. We show that the promigration effects of Tcf3 are non-cell autonomous and occur independently of its ability to interact with β-catenin. Finally, we identify lipocalin-2 as the key secreted factor downstream of Tcf3 that promotes cell migration in vitro and wound healing in vivo. Our findings provide new insights into the molecular controls of wound-associated cell migration and identify potential therapeutic targets for the treatment of defective wound repair.

Suggested Citation

  • Qi Miao & Amy T. Ku & Yudai Nishino & Jeffrey M. Howard & Ajay S. Rao & Timothy M. Shaver & Gloria E. Garcia & Diep N. Le & Kristen L. Karlin & Thomas F. Westbrook & Valeria Poli & Hoang Nguyen, 2014. "Tcf3 promotes cell migration and wound repair through regulation of lipocalin 2," Nature Communications, Nature, vol. 5(1), pages 1-15, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5088
    DOI: 10.1038/ncomms5088
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