Donato Alice, Belluzzi Elisa, Mattiuzzo Elena, Venerando Rina, Cadamuro Massimiliano, Ruggieri Pietro, Vindigni Vincenzo, Brun Paola
Histology Unit, Department of Molecular Medicine, University of Padova, 35121 Padova, Italy.
Musculoskeletal Pathology and Oncology Laboratory, Department of Surgery, Oncology and Gastroenterology (DiSCOG), University of Padova, 35128 Padova, Italy.
Polymers (Basel). 2022 Apr 29;14(9):1817. doi: 10.3390/polym14091817.
Inflammation and the accumulation of reactive oxygen species (ROS) play an important role in the structural and functional modifications leading to skin ageing. The reduction of inflammation, cellular oxidation and dermal extracellular matrix (ECM) alterations may prevent the ageing process. The aim of this study is to investigate the expression of pro-inflammatory markers and ECM molecules in human dermal fibroblasts derived from young and middle-aged women and the effects of lactose-modified chitosan (Chitlac, CTL), alone or in combination with mid-MW hyaluronan (HA), using an in vitro model of inflammation. To assess the response of macrophage-induced inflamed dermal fibroblasts to HA and CTL, changes in cell viability, pro-inflammatory mediators, MMPs and ECM molecules expression and intracellular ROS generation are analysed at gene and protein levels. The expression of pro-inflammatory markers, galectins, MMP-3 and ECM molecules is age-related. CTL, HA and their combination counteracted the oxidative damage, stimulating the expression of ECM molecules, and, when added to inflamed cells, restored the baseline levels of IL-1β, TNF-α, GAL-1, GAL-3 and MMP-3. In conclusion, HA and CTL mixture attenuated the macrophage-induced inflammation, inhibited the MMP-3 expression, exhibited the anti-oxidative effects and exerted a pro-regenerative effect on ECM.
炎症和活性氧(ROS)的积累在导致皮肤老化的结构和功能改变中起重要作用。减轻炎症、细胞氧化和真皮细胞外基质(ECM)改变可能会预防衰老过程。本研究的目的是利用炎症体外模型,研究年轻和中年女性来源的人真皮成纤维细胞中促炎标志物和ECM分子的表达,以及乳糖修饰壳聚糖(Chitlac,CTL)单独或与中分子量透明质酸(HA)联合使用的效果。为了评估巨噬细胞诱导的炎症性真皮成纤维细胞对HA和CTL的反应,在基因和蛋白质水平分析细胞活力、促炎介质、基质金属蛋白酶(MMPs)和ECM分子表达以及细胞内ROS生成的变化。促炎标志物、半乳糖凝集素、MMP-3和ECM分子的表达与年龄相关。CTL、HA及其组合可抵消氧化损伤,刺激ECM分子的表达,并且当添加到炎症细胞中时,可恢复IL-1β、TNF-α、GAL-1、GAL-3和MMP-3的基线水平。总之,HA和CTL混合物减轻了巨噬细胞诱导的炎症,抑制了MMP-3的表达,表现出抗氧化作用,并对ECM发挥了促再生作用。