Department of Pharmaceutical Sciences, University of Milan, Via L. Mangiagalli 25, 20133, Milan, Italy.
Intercos S.p.A., Via Marconi 84, 20864, Agrate Brianza, MB, Italy.
J Pharm Biomed Anal. 2020 Jun 5;185:113199. doi: 10.1016/j.jpba.2020.113199. Epub 2020 Feb 29.
Hyaluronic acid (HA) is physiologically synthesized by several human cells types but it is also a widespread ingredient of commercial products, from pharmaceuticals to cosmetics. Despite its extended use, the precise intra- and extra-cellular effects of HA at low-molecular-weight (LWM-HA) are currently unclear. At this regard, the aim of this study is to in-depth identify and quantify proteome's changes in normal human dermal fibroblasts after 24 h treatment with 0.125, 0.25 and 0.50 % LMW-HA (20-50 kDa) respectively, vs controls. To do this, a label-free quantitative proteomic approach based on high-resolution mass spectrometry was used. Overall, 2328 proteins were identified of which 39 significantly altered by 0.125 %, 149 by 0.25 % and 496 by 0.50 % LMW-HA. Protein networking studies indicated that the biological effects involve the enhancement of intracellular activity at all concentrations, as well as the extracellular matrix reorganization, proteoglycans and collagen biosynthesis. Moreover, the cell's wellness was confirmed, although mild inflammatory and immune responses were induced at the highest concentration. The more complete comprehension of intra- and extra-cellular effects of LMW-HA here provided by an advanced analytical approach and protein networking will be useful to further exploit its features and improve current formulations.
透明质酸（HA）是由几种人体细胞类型生理合成的，但它也是商业产品（从药物到化妆品）的广泛成分。尽管其用途广泛，但低分子量（LWM-HA）HA 的内在和外在细胞作用目前尚不清楚。在这方面，本研究的目的是深入识别和量化正常人类皮肤成纤维细胞在 24 小时分别用 0.125%、0.25%和 0.50%的 LWM-HA（20-50 kDa）处理后的蛋白质组变化，与对照组相比。为此，使用了基于高分辨率质谱的无标记定量蛋白质组学方法。总体而言，鉴定出了 2328 种蛋白质，其中 39 种蛋白质被 0.125%、149 种蛋白质被 0.25%和 496 种蛋白质被 0.50%的 LWM-HA 显著改变。蛋白质网络研究表明，生物学效应涉及所有浓度下细胞内活性的增强，以及细胞外基质的重组、蛋白聚糖和胶原蛋白的生物合成。此外，尽管在最高浓度下诱导了轻度炎症和免疫反应，但细胞的健康状况得到了证实。通过先进的分析方法和蛋白质网络提供的对 LWM-HA 内在和外在细胞作用的更全面理解，将有助于进一步利用其特性并改进当前的配方。
