Edinburgh Research Explorer

Macrophage Wnt-Calcineurin-Flt1 signaling regulates mouse wound angiogenesis and repair

Research output: Contribution to journalArticle

  • James A Stefater
  • Sujata Rao
  • Katie Bezold
  • Alfred C Aplin
  • Roberto F Nicosia
  • Jeffrey W Pollard
  • Napoleone Ferrara
  • Richard A Lang

Related Edinburgh Organisations

Original languageEnglish
Pages (from-to)2574-8
Number of pages5
Issue number13
Publication statusPublished - 28 Mar 2013


The treatment of festering wounds is one of the most important aspects of medical care. Macrophages are important components of wound repair, both in fending off infection and in coordinating tissue repair. Here we show that macrophages use a Wnt-Calcineurin-Flt1 signaling pathway to suppress wound vasculature and delay repair. Conditional mutants deficient in both Wntless/GPR177, the secretory transporter of Wnt ligands, and CNB1, the essential component of the nuclear factor of activated T cells dephosporylation complex, displayed enhanced angiogenesis and accelerated repair. Furthermore, in myeloid-like cells, we show that noncanonical Wnt activates Flt1, a naturally occurring inhibitor of vascular endothelial growth factor-A-mediated angiogenesis, but only when calcineurin function is intact. Then, as expected, conditional deletion of Flt1 in macrophages resulted in enhanced wound angiogenesis and repair. These results are consistent with the published link between enhanced angiogenesis and enhanced repair, and establish novel therapeutic approaches for treatment of wounds.

    Research areas

  • Animals, Calcineurin, Cells, Cultured, Dermis, Macrophages, Mice, Mice, Transgenic, Neovascularization, Physiologic, Protein Subunits, Vascular Endothelial Growth Factor Receptor-1, Wnt Proteins, Wnt Signaling Pathway, Wound Healing

ID: 12627485