title: The role of mast cells in cutaneous wound healing in streptozotocin-induced diabetic mice.
abstract: Mast cells (MCs) reside in cutaneous tissue, and an increment of MCs is suggested to induce vascular regression in the process of wound healing. To clarify participation of MCs in diabetic cutaneous wound healing, we created an excisional wound on diabetic mice 4 weeks after streptozotocin injections and subsequently investigated the healing processes for 49 days, comparing them with control mice. The rate of wound closure was not markedly different between the diabetic and control mice. In the proliferative phase at days 7 and 14, neovascularization in the wound was weaker in diabetic mice than in control mice. In the remodeling phase at day 21 and afterward, rapid vascular regression occurred in control mice; however, neovascularization was still observed in diabetic mice where the number of vessels in granulation tissues was relatively higher than in control mice. In the remodeling phase of the control mice, MCs within the wound began to increase rapidly and resulted in considerable accumulation, whereas the increment of MCs was delayed in diabetic mice. In addition, the number of fibroblast growth factor (FGF)- or vascular endothelial growth factor (VEGF)-immunopositive hypertrophic fibroblast-like spindle cells and c-Kit-positive/VEGFR2-positive/FcεRIα-negative endothelial progenitor cells (EPCs) were higher in diabetic wounds. In conclusion, neovascularization in the proliferative phase and vascular regression in the remodeling phase were impaired in diabetic mice. The delayed increment of MCs and sustained angiogenic stimuli by fibroblast-like spindle cells and EPCs may inhibit vascular regression in the remodeling phase and impair the wound-healing process in diabetic mice.
authors.affiliation: Department of Pharmacology, Shimane University School of Medicine, 89-1 Enya-cho, Izumo, Shimane, 693-8501, Japan, yakurign@med.shimane-u.ac.jp.
authors.forename: Yoriko
authors.initials: Y
authors.lastname: Nishikori
authors.forename: Naotaka
authors.initials: N
authors.lastname: Shiota
authors.forename: Hideki
authors.initials: H
authors.lastname: Okunishi
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D066026:Endothelial Progenitor Cells / Q000378:metabolism / Q000473:pathology; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology*; D008813:Mice, Inbred ICR; D009389:Neovascularization, Pathologic; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D013311:Streptozocin; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D066253:Vascular Remodeling; D014945:Wound Healing
chemical_list: D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D013311:Streptozocin; D005346:Fibroblast Growth Factors; C000592875:Kdr protein, mouse; D019009:Proto-Oncogene Proteins c-kit; D040301:Vascular Endothelial Growth Factor Receptor-2