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用于促进皮肤伤口愈合的生物活性低分子量角蛋白水解物

Bioactive Low Molecular Weight Keratin Hydrolysates for Improving Skin Wound Healing.

作者信息

Olariu Laura, Dumitriu Brindusa Georgiana, Gaidau Carmen, Stanca Maria, Tanase Luiza Mariana, Ene Manuela Diana, Stanculescu Ioana-Rodica, Tablet Cristina

机构信息

SC Biotehnos SA, 3-5 Gorunului Street, 075100 Otopeni, Romania.

Academy of Romanian Scientists, 3 Ilfov Street, 030167 Bucharest, Romania.

出版信息

Polymers (Basel). 2022 Mar 11;14(6):1125. doi: 10.3390/polym14061125.

Abstract

Keratin biomaterials with high molecular weights were intensively investigated but few are marketed due to complex methods of extraction and preparation and limited understanding of their influence on cells behavior. In this context the aim of this research was to elucidate decisive molecular factors for skin homeostasis restoration induced by two low molecular weight keratin hydrolysates extracted and conditioned through a simple and green method. Two keratin hydrolysates with molecular weights of 3758 and 12,400 Da were physico-chemically characterized and their structure was assessed by circular dichroism (CD) and FTIR spectroscopy in view of bioactive potential identification. Other investigations were focused on several molecular factors: α1, α2 and β1 integrin mediated signals, cell cycle progression in pro-inflammatory conditions (TNFα/LPS stimulated keratinocytes and fibroblasts) and ICAM-1/VCAM-1 inhibition in human vascular endothelial cells. Flow cytometry techniques demonstrated a distinctive pattern of efficacy: keratin hydrolysates over-expressed α1 and α2 subunits, responsible for tight bounds between fibroblasts and collagen or laminin 1; both actives stimulated the epidermal turn-over and inhibited VCAM over-expression in pro-inflammatory conditions associated with bacterial infections. Our results offer mechanistic insights in wound healing signaling factors modulated by the two low molecular weight keratin hydrolysates which still preserve bioactive secondary structure.

摘要

高分子量角蛋白生物材料受到了广泛研究,但由于提取和制备方法复杂,以及对其对细胞行为影响的了解有限,很少有产品上市。在此背景下,本研究旨在阐明通过简单绿色方法提取和处理的两种低分子量角蛋白水解产物诱导皮肤稳态恢复的决定性分子因素。对分子量分别为3758和12400 Da的两种角蛋白水解产物进行了物理化学表征,并通过圆二色性(CD)和傅里叶变换红外光谱(FTIR)对其结构进行了评估,以确定其生物活性潜力。其他研究集中在几个分子因素上:α1、α2和β1整合素介导的信号、促炎条件下(TNFα/LPS刺激的角质形成细胞和成纤维细胞)的细胞周期进程以及人血管内皮细胞中ICAM-1/VCAM-1的抑制。流式细胞术技术显示出独特的功效模式:角蛋白水解产物过表达α1和α2亚基,这两个亚基负责成纤维细胞与胶原蛋白或层粘连蛋白1之间的紧密结合;两种活性成分均刺激表皮更新,并在与细菌感染相关的促炎条件下抑制VCAM的过表达。我们的结果为两种低分子量角蛋白水解产物调节伤口愈合信号因子提供了机制性见解,这两种水解产物仍保留生物活性二级结构。

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