title: CXCR4 antagonist AMD3100 accelerates impaired wound healing in diabetic mice.
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.
authors: Feinberg Cardiovascular Research Institute, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors: Yukihide
authors: Y
authors: Nishimura
authors: Masaaki
authors: M
authors: Ii
authors: Gangjian
authors: G
authors: Qin
authors: Hiromichi
authors: H
authors: Hamada
authors: Jun
authors: J
authors: Asai
authors: Hideya
authors: H
authors: Takenaka
authors: Haruki
authors: H
authors: Sekiguchi
authors: Marie-Ange
authors: MA
authors: Renault
authors: Kentaro
authors: K
authors: Jujo
authors: Norito
authors: N
authors: Katoh
authors: Saburo
authors: S
authors: Kishimoto
authors: Aiko
authors: A
authors: Ito
authors: Christine
authors: C
authors: Kamide
authors: John
authors: J
authors: Kenny
authors: Meredith
authors: M
authors: Millay
authors: Sol
authors: S
authors: Misener
authors: Tina
authors: T
authors: Thorne
authors: Douglas W
authors: DW
authors: Losordo
mesh_terms: D000818:Animals; D001596:Benzylamines; D002196:Capillaries / Q000254:growth & development; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D003094:Collagen / Q000096:biosynthesis; D000080027:Cyclams; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D006571:Heterocyclic Compounds / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010587:Phagocytosis / Q000187:drug effects; D020574:Proto-Oncogene Proteins c-sis / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D054411:Receptors, Leptin / Q000172:deficiency; D012867:Skin / Q000187:drug effects* / Q000293:injuries* / Q000473:pathology; D013234:Stem Cells; D016896:Treatment Outcome; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D001596:Benzylamines; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D000080027:Cyclams; D006571:Heterocyclic Compounds; D020574:Proto-Oncogene Proteins c-sis; D019718:Receptors, CXCR4; D054411:Receptors, Leptin; D003094:Collagen; C088327:plerixafor