Several studies have shown the importance of purinergic signaling in various inflammatory dis-eases. In diabetes mellitus, there is an increase in the activity of some nucleotidases suggesting that this signaling may be affected in the diabetic skin. Thus, the aim of our study was to inves-tigate the effect of ADP on wound healing in diabetic skin. Swis and C57BL/6 mice were pharmacologic induced to type 1 diabetes and submitted to a full-thickness excisional wound model to evaluate the effect of ADP as a topic treatment. Adenosine diphosphate accelerated cutaneous wound healing, improved the new tissue formation, and increased collagen deposit by positively modulating P2Y1 and P2Y12 and TGF-β production. In parallel, ADP reduced reactive oxygen species production and TNF-𝛼 levels, while increased IFNγ, IL-10 and IL-13 levels in the skin. Also, ADP induced the migration of neutrophils, eosinophils, mast cells, TCRγ4+, and TCRγ5+ cells while reduced Treg cells towards the lesion at day 7. In accordance, ADP increased the proliferation and migration of fibroblast, induced myofibroblast differentiation and keratinocyte proliferation in a P2Y12-dependent manner. We provide the first evidence of ADP acting as a potent mediator on skin wound resolution and a possible therapeutic approach for diabetic patients worldwide.

中文翻译：

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二磷酸腺苷通过激活P2Y1和P2Y12受体促进糖尿病小鼠的伤口愈合

几项研究表明嘌呤能信号传导在各种炎性疾病中的重要性。在糖尿病中，某些核苷酸酶的活性增加，表明该信号传导可能在糖尿病皮肤中受到影响。因此，我们研究的目的是研究ADP对糖尿病皮肤伤口愈合的作用。Swis和C57BL / 6小鼠被药理学诱导为1型糖尿病，并接受了全层切除伤口模型以评估ADP作为主题治疗的效果。二磷酸腺苷通过正向调节P2Y1和P2Y12以及TGF-β的产生，加速了皮肤伤口的愈合，改善了新组织的形成，并增加了胶原蛋白的沉积。同时，ADP减少了活性氧的产生和TNF-α的水平，同时增加了皮肤中IFNγ，IL-10和IL-13的水平。也，在第7天，ADP诱导嗜中性粒细胞，嗜酸性粒细胞，肥大细胞，TCRγ4+和TCRγ5+细胞迁移，同时减少Treg细胞向病变处转移。相应地，ADP增强了P2Y12-P2中成纤维细胞的增殖和迁移，诱导了成纤维细胞的分化和角质形成细胞的增殖。依赖方式。我们提供了第一个证据，证明ADP可以有效解决皮肤伤口愈合问题，并为全球糖尿病患者提供可能的治疗方法。