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Blood. 2013 Mar 28;121(13):2574-8. doi: 10.1182/blood-2012-06-434621. Epub 2013 Jan 9.

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

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1
The Visual Systems Group, Divisions of Pediatric Ophthalmology and Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

Erratum in

  • Blood. 2013 Sep 26;122(13):2290.

Abstract

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.

PMID:
23303818
PMCID:
PMC3612865
DOI:
10.1182/blood-2012-06-434621
[Indexed for MEDLINE]
Free PMC Article
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