Activated protein C prevents inflammation yet stimulates angiogenesis to promote cutaneous wound healing
Activated protein C prevents inflammation yet stimulates angiogenesis to promote cutaneous wound healing
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DOI：
10.1111/j.1067-1927.2005.00130311.x
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发表时间：
2005-05-01
影响因子：
2.9
通讯作者：
March, L
中科院分区：
文献类型：
--
作者：
Jackson, CJ;Xue, ML;March, L
活化蛋白C（APC）是一种丝氨酸蛋白酶，在生理抗凝中起核心作用，最近已被证明是一种有效的抗炎介质。使用培养的人类细胞，我们在这里显示，APC上调血管生成的促进剂基质金属蛋白酶-2在皮肤成纤维细胞和脐静脉内皮细胞，血管内皮生长因子在角质形成细胞和成纤维细胞，和单核细胞趋化蛋白-1在成纤维细胞。在鸡胚绒毛尿囊膜试验中，APC通过显着刺激血管生成以及促进再上皮化来促进伤口愈合的肉芽/重塑阶段。在全层大鼠皮肤愈合模型中，与盐水对照相比，APC的单次局部应用增强了伤口愈合。APC处理的伤口在第7天具有显著更多的血管，并且在第4天和第7天具有显著更低的中性粒细胞浸润。广谱基质金属蛋白酶GM 6001抑制APC促进伤口愈合的能力。总之，我们的研究结果表明，APC促进皮肤伤口愈合通过一个复杂的机制，涉及刺激血管生成和抑制炎症。APC的这些独特性质使其成为促进慢性伤口愈合的有吸引力的治疗剂。
Activated protein C (APC) is a serine protease that plays a central role in physiological anticoagulation, and has more recently been shown to be a potent anti-inflammatory mediator. Using cultured human cells, we show here that APC up-regulates the angiogenic promoters matrix metalloproteinase-2 in skin fibroblasts and umbilical vein endothelial cells, vascular endothelial growth factor in keratinocytes and fibroblasts, and monocyte chemoattractant protein-1 in fibroblasts. In the chick embryo chorioallantoic membrane assay, APC promoted the granulation/remodeling phases of wound healing by markedly stimulating angiogenesis as well as promoting reepithelialization. In a full-thickness rat skin-healing model, a single topical application of APC enhanced wound healing compared to saline control. APC-treated wounds had markedly more blood vessels on day 7 and a significantly lower infiltration of neutrophils at days 4 and 7. The broad spectrum matrix metallo-proteinas, GM6001, prevented the ability of APC to promote wound healing. In summary, our results show that APC promotes cutaneous wound healing via a complex mechanism involving stimulation of angiogenesis and inhibition of inflammation. These unique properties of APC make it an attractive therapeutic agent to promote the healing of chronic wounds.