The role of mast cells in cutaneous wound healing in streptozotocin-induced diabetic mice
The role of mast cells in cutaneous wound healing in streptozotocin-induced diabetic mice
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DOI：
10.1007/s00403-014-1496-0
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发表时间：
2014-11-01
影响因子：
3
通讯作者：
Okunishi, Hideki
中科院分区：
文献类型：
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作者：
Nishikori, Yoriko;Shiota, Naotaka;Okunishi, Hideki
肥大细胞（MC）存在于皮肤组织中，并且MC的增加被认为在伤口愈合过程中诱导血管消退。为了阐明MCs参与糖尿病皮肤伤口愈合，我们在链脲佐菌素注射后4周对糖尿病小鼠创建了切除伤口，随后研究了49天的愈合过程，并将其与对照小鼠进行比较。糖尿病小鼠和对照小鼠的伤口闭合率没有显著差异。在第7天和第14天的增殖期，糖尿病小鼠伤口中的新血管形成比对照小鼠弱。在第21天及之后的重塑阶段，对照小鼠中发生快速血管消退;然而，在糖尿病小鼠中仍然观察到新血管形成，其中肉芽组织中的血管数量相对高于对照小鼠。在对照组小鼠的伤口重塑阶段，MC开始迅速增加，并导致相当大的积累，而MC的增加在糖尿病小鼠延迟。此外，成纤维细胞生长因子（FGF）或血管内皮生长因子（VEGF）免疫阳性肥大成纤维细胞样梭形细胞和c-Kit阳性/VEGFR 2阳性/Fc β RI α阴性内皮祖细胞（EPC）的数量在糖尿病伤口中较高。总之，糖尿病小鼠增殖期的新血管形成和重塑期的血管退化受损。MCs的延迟增加和成纤维细胞样梭形细胞和EPCs的持续血管生成刺激可能会抑制糖尿病小鼠在重塑阶段的血管退化，并损害伤口愈合过程。
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/Fc epsilon RI alpha-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.