Belvedere Raffaella, Bizzarro Valentina, Parente Luca, Petrella Francesco, Petrella Antonello
Department of Pharmacy, University of Salerno, via Giovanni Paolo II 132, 84084 Fisciano (Salerno), Italy.
Primary Care-Wound Care Service, Health Local Agency Naples 3 South, Via Libertà 42, 80055 Portici (Napoli), Italy.
Int J Mol Sci. 2017 Jul 25;18(8):1614. doi: 10.3390/ijms18081614.
Glycosaminoglycans are polysaccharides of the extracellular matrix supporting skin wound closure. Mesoglycan is a mixture of glycosaminoglycans such as chondroitin-, dermatan-, heparan-sulfate and heparin and is the main component of Prisma Skin, a pharmaceutical device developed by Mediolanum Farmaceutici S.p.a. Here, we show the in vitro effects of this device in the new vessels formation by endothelial cells, since angiogenesis represents a key moment in wound healing. We found a strong increase of migration and invasion rates of these cells treated with mesoglycan and Prisma Skin which mediate the activation of the pathway triggered by CD44 receptor. Furthermore, endothelial cells form longer capillary-like structures with a great number of branches, in the presence of the same treatments. Thus, the device, thanks to the mesoglycan, leads the cells to the Endothelial-to-Mesenchymal Transition, suggesting the switch to a fibroblast-like phenotype, as shown by immunofluorescence assays. Finally, we found that mesoglycan and Prisma Skin inhibit inflammatory reactions such as nitric oxide secretion and NF-κB nuclear translocation in endothelial cells and Tumor Necrosis Factor-α production by macrophages. In conclusion, based on our data, we suggest that Prisma Skin may be able to accelerate angiogenesis in skin wound healing, and regulate inflammation avoiding chronic, thus pathological, responses.
糖胺聚糖是细胞外基质中的多糖，有助于皮肤伤口愈合。间糖胺聚糖是一种糖胺聚糖混合物，如硫酸软骨素、硫酸皮肤素、硫酸乙酰肝素和肝素，是Mediolanum Farmaceutici S.p.a.研发的一种药物装置Prisma Skin的主要成分。在此，我们展示了该装置对内皮细胞新血管形成的体外作用，因为血管生成是伤口愈合的关键阶段。我们发现，用间糖胺聚糖和Prisma Skin处理的这些细胞的迁移和侵袭率显著增加，这介导了由CD44受体触发的信号通路的激活。此外，在相同处理条件下，内皮细胞会形成更多分支的更长的毛细血管样结构。因此，该装置借助间糖胺聚糖，使细胞发生内皮-间充质转化，提示细胞转变为成纤维细胞样表型，免疫荧光分析证实了这一点。最后，我们发现间糖胺聚糖和Prisma Skin可抑制内皮细胞中的一氧化氮分泌和NF-κB核转位等炎症反应，以及巨噬细胞产生肿瘤坏死因子-α。总之，根据我们的数据，我们认为Prisma Skin或许能够加速皮肤伤口愈合中的血管生成，并调节炎症反应，避免慢性进而病理性反应的发生。
