CXCR4 antagonist AMD3100 accelerates impaired wound healing in diabetic mice.
CXCR4 antagonist AMD3100 accelerates impaired wound healing in diabetic mice.
复制标题
DOI：
10.1038/jid.2011.356
复制
发表时间：
2012-03
影响因子：
6.5
通讯作者：
Losordo, Douglas W.
中科院分区：
文献类型：
--
作者：
Nishimura, Yukihide;Ii, Masaaki;Qin, Gangjian;Hamada, Hiromichi;Asai, Jun;Takenaka, Hideya;Sekiguchi, Haruki;Renault, Marie-Ange;Jujo, Kentaro;Katoh, Norito;Kishimoto, Saburo;Ito, Aiko;Kamide, Christine;Kenny, John;Millay, Meredith;Misener, Sol;Thorne, Tina;Losordo, Douglas W.
AMD 3100对CXC趋化因子受体4（CXCR 4）的拮抗作用通过增加骨髓中内皮祖细胞（EPC）向再生血管系统的募集来改善心肌梗死后的心脏性能。我们研究了AMD 3100是否可以通过类似的机制加速糖尿病受损的伤口愈合。在瘦素受体缺陷小鼠的背部上制作皮肤伤口，并用AMD 3100或盐水处理。治疗后14天，AMD 3100治疗组小鼠的伤口闭合明显更完全（AMD 3100：87.0± 2.6%，生理盐水：33.1±1.8%; P<0.0001），并伴有更大的胶原纤维形成、毛细血管密度、含平滑肌的血管密度和单核细胞/巨噬细胞浸润。治疗后第7天，AMD 3100与较高的循环EPC和巨噬细胞计数以及伤口床中基质细胞衍生因子1和血小板衍生生长因子B的mRNA水平显著上调相关。AMD 3100还促进巨噬细胞增殖和吞噬作用以及糖尿病小鼠原代真皮成纤维细胞和3 T3成纤维细胞的迁移和增殖，这些细胞表达非常少的CXCR 4。总之，AMD 3100的单次局部应用通过增加细胞因子产生、动员骨髓EPCs和增强成纤维细胞和单核细胞/巨噬细胞的活性，从而增加血管生成和血管生成，促进糖尿病小鼠的伤口愈合。并非所有AMD 3100介导的效应都是通过CXCR 4拮抗作用产生的。
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.
登录
查看更多内容
影响因子：
6.5
作者：
Asai, Jun;Takenaka, Hideya;Kishimoto, Saburo
通讯作者：
Kishimoto, Saburo
影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
37.8
作者：
Asai, Jun;Takenaka, Hideya;Losordo, Douglas W.
通讯作者：
Losordo, Douglas W.
影响因子：
--
作者：
Brem, H;Balledux, J;Hollier, L
通讯作者：
Hollier, L
影响因子：
15.9
作者：
Gallagher, Katherine A.;Liu, Zhao-Jun;Velazquez, Omaida C.
通讯作者：
Velazquez, Omaida C.