CXCR4 antagonist AMD3100 accelerates impaired wound healing in diabetic mice

Yukihide Nishimura, Masaaki Ii, Gangjian Qin, Hiromichi Hamada, Jun Asai, Hideya Takenaka, Haruki Sekiguchi, Marie Ange Renault, Kentaro Jujo, Norito Katoh, Saburo Kishimoto, Aiko Ito, Christine Kamide, John Kenny, Meredith Millay, Sol Misener, Tina Thorne, Douglas W. Losordo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

The antagonism of CXC-chemokine receptor 4 (CXCR4) with AMD3100 improves cardiac performance after myocardial infarction by augmenting the recruitment of endothelial progenitor cells (EPCs) from the bone marrow to the regenerating vasculature. We investigated whether AMD3100 may accelerate diabetes-impaired wound healing through a similar mechanism. Skin wounds were made on the backs of leptin receptor-deficient mice and treated with AMD3100 or saline. Fourteen days after treatment, wound closure was significantly more complete in AMD3100-treated mice (AMD3100: 87.0±2.6%, saline: 33.1±1.8%; P<0.0001) and was accompanied by greater collagen fiber formation, capillary density, smooth muscle-containing vessel density, and monocyte/macrophage infiltration. On day 7 after treatment, AMD3100 was associated with higher circulating EPC and macrophage counts, and with significantly upregulated mRNA levels of stromal cell-derived factor 1 and platelet-derived growth factor B in the wound bed. AMD3100 also promoted macrophage proliferation and phagocytosis and the migration and proliferation of diabetic mouse primary dermal fibroblasts and 3T3 fibroblasts, which express very little CXCR4. In conclusion, a single topical application of AMD3100 promoted wound healing in diabetic mice by increasing cytokine production, mobilizing bone marrow EPCs, and enhancing the activity of fibroblasts and monocytes/macrophages, thereby increasing both angiogenesis and vasculogenesis. Not all of the AMD3100-mediated effects evolved through CXCR4 antagonism.

Original languageEnglish (US)
Pages (from-to)711-720
Number of pages10
JournalJournal of Investigative Dermatology
Volume132
Issue number3 PART 1
DOIs
StatePublished - Mar 2012

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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