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

Nat Commun. 2014 Jun 9:5:4088. doi: 10.1038/ncomms5088.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / metabolism*
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Movement / genetics*
  • Cell Movement / physiology
  • Keratinocytes*
  • Lipocalin-2
  • Lipocalins / metabolism*
  • Mice
  • Mice, Knockout
  • Oncogene Proteins / metabolism*
  • Re-Epithelialization / genetics*
  • Re-Epithelialization / physiology
  • STAT3 Transcription Factor / metabolism*
  • Skin / cytology
  • Skin / metabolism*
  • Wound Healing / genetics*
  • Wound Healing / physiology
  • beta Catenin / metabolism

Substances

  • Acute-Phase Proteins
  • Basic Helix-Loop-Helix Transcription Factors
  • CTNNB1 protein, mouse
  • Lipocalin-2
  • Lipocalins
  • Oncogene Proteins
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Tcf3 protein, mouse
  • beta Catenin
  • Lcn2 protein, mouse