Department of Biomedical Chemistry, Faculty of Chemistry, University of Gdańsk, 80-308 Gdańsk, Poland.
Laboratory of Tissue Engineering and Regenerative Medicine, Department of Embryology, Medical University of Gdańsk, 80-210 Gdańsk, Poland.
Molecules. 2020 Jun 23;25(12):2884. doi: 10.3390/molecules25122884.
Regeneration and wound healing are vital to tissue homeostasis and organism survival. One of the biggest challenges of today's science and medicine is finding methods and factors to stimulate these processes in the human body. Effective solutions to promote regenerative responses will accelerate advances in tissue engineering, regenerative medicine, transplantology, and a number of other clinical specialties. In this study, we assessed the potential efficacy of a synthetic hexapeptide, RDKVYR, for the stimulation of tissue repair and wound healing. The hexapeptide is marketed under the name "Imunofan" (IM) as an immunostimulant. IM displayed stability in aqueous solutions, while in plasma it was rapidly bound by albumins. Structural analyses demonstrated the conformational flexibility of the peptide. Tests in human fibroblast and keratinocyte cell lines showed that IM exerted a statistically significant ( < 0.05) pro-proliferative activity (30-40% and 20-50% increase in proliferation of fibroblast and keratinocytes, respectively), revealed no cytotoxicity over a vast range of concentrations ( < 0.05), and had no allergic properties. IM was found to induce significant transcriptional responses, such as enhanced activity of genes involved in active DNA demethylation ( < 0.05) in fibroblasts and activation of genes involved in immune responses, migration, and chemotaxis in adipose-derived stem cells derived from surgery donors. Experiments in a model of ear pinna injury in mice indicated that IM moderately promoted tissue repair (8% in BALB/c and 36% in C57BL/6 in comparison to control).
再生和伤口愈合对于组织内稳态和生物体的生存至关重要。当今科学和医学面临的最大挑战之一是寻找方法和因素来刺激人体中的这些过程。有效的促进再生反应的解决方案将加速组织工程学、再生医学、移植学和许多其他临床专业的进展。在这项研究中,我们评估了一种合成六肽 RDKVYR 刺激组织修复和伤口愈合的潜力。这种六肽以“Imunofan”(IM)的名称作为免疫刺激剂出售。IM 在水溶液中稳定,而在血浆中则迅速与白蛋白结合。结构分析表明该肽具有构象灵活性。在人成纤维细胞和角质形成细胞系中的测试表明,IM 表现出统计学上显著的(<0.05)促增殖活性(成纤维细胞和角质形成细胞的增殖分别增加 30-40%和 20-50%),在广泛的浓度范围内(<0.05)没有细胞毒性,并且没有过敏特性。IM 被发现诱导显著的转录反应,例如在成纤维细胞中增强涉及主动 DNA 去甲基化的基因的活性(<0.05),以及在来自手术供体的脂肪来源干细胞中激活涉及免疫反应、迁移和趋化性的基因。在小鼠耳瓣损伤模型中的实验表明,IM 适度促进组织修复(与对照组相比,BALB/c 中为 8%,C57BL/6 中为 36%)。