Protective Effect of MFG-E8 after Cutaneous Ischemia-Reperfusion Injury
Protective Effect of MFG-E8 after Cutaneous Ischemia-Reperfusion Injury
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DOI：
10.1038/jid.2014.515
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发表时间：
2015-04-01
影响因子：
6.5
通讯作者：
Motegi, Sei-ichiro
中科院分区：
文献类型：
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作者：
Uchiyama, Akihiko;Yamada, Kazuya;Motegi, Sei-ichiro
我们最近证实，分泌的糖蛋白和整合素配体MFG-E8通过促进血管生成促进皮肤伤口愈合。几项研究已经确定了MFG-E8在脑、肾和肝脏缺血再灌注(I/R)损伤的调节中的潜在作用。我们的目的是使用皮肤I/R损伤皮肤压疮的小鼠模型来评估MFG-E8在皮肤溃疡形成中的作用。将背部皮肤夹在两个磁极板之间12小时，然后取出磁极板，进行皮肤I/R。MFG-E8在缺血时真皮表达增加，再灌流后表达降低。I/R再灌注区给予重组(R)MFG-E8可显著抑制皮肤压疮的形成，增加创面CD31(+)血管和NG2(+)周细胞的数量。RMFG-E8可减少创面M1巨噬细胞数和促炎介质单核细胞趋化蛋白-1、诱导型一氧化氮合酶、IL-6、肿瘤坏死因子-α和IL-1β的含量。结论：MFG-E8可能通过调节血管生成和炎症反应抑制皮肤I/R损伤所致压疮的形成。外源性应用MFG-E8可能对皮肤I/R损伤有治疗潜力，包括压疮和雷诺现象所致的指端溃疡。
We recently demonstrated that the secreted glycoprotein and integrin-ligand MFG-E8 promotes cutaneous wound healing by enhancing angiogenesis. Several studies have identified potential roles for MFG-E8 in regulation of ischemia-reperfusion (I/R) injury in the brain, kidney, and liver. Our objective was to assess the role of MFG-E8 in the formation of skin ulcers using a murine model of cutaneous I/R injury cutaneous pressure ulcers. Cutaneous I/R was performed by trapping the dorsal skin between two magnetic plates for 12 hours, followed by plate removal. Expression of MFG-E8 increased in the dermis during ischemia, and then decreased after reperfusion. Administration of recombinant (r)MFG-E8 in I/R areas at the beginning of reperfusion significantly inhibited the formation of cutaneous pressure ulcers, and the number of CD31(+) vessel and NG2(+) pericytes in wounds were increased in I/R mice treated with rMFG-E8. The number of M1 macrophages and the amount of proinflammatory mediators monocyte chemotactic protein-1,induced nitric oxide synthase, IL-6, tumor necrosis factor-alpha; and IL-1 beta in the wound area were reduced by the administration of rMFG-E8. We conclude that MFG-E8 may inhibit the formation of pressure ulcers induced by cutaneous I/R injury by regulating angiogenesis and inflammation. Exogenous application of MFG-E8 might have therapeutic potential for cutaneous I/R injuries, including decubitus ulcers and Raynaud's phenomenon induced digital ulcers.