Experimental Dermatology and Skin Biology Group, Ramon y Cajal Institute for Health Research (IRYCIS), Ramón y Cajal University Hospital, 28034 Madrid, Spain.
Instituto de Investigaciones Biosanitarias, Facultad de Ciencias Experimentales, Universidad Francisco de Vitoria, 28223 Pozuelo de Alarcón, Spain.
Int J Mol Sci. 2019 Apr 9;20(7):1741. doi: 10.3390/ijms20071741.
Glycosaminoglycans (GAGs) and associated proteoglycans have important functions in homeostatic maintenance and regenerative processes (e.g., wound repair) of the skin. However, little is known about the role of these molecules in the regulation of the hair follicle cycle. Here we report that growing human hair follicles ex vivo in a defined GAG hydrogel mimicking the dermal matrix strongly promotes sustained cell survival and maintenance of a highly proliferative phenotype in the hair bulb and suprabulbar regions. This significant effect is associated with the activation of WNT/β-catenin signaling targets (CCDN1, AXIN2) and with the expression of stem cell markers (CK15, CD34) and growth factors implicated in the telogen/anagen transition (TGFβ2, FGF10). As a whole, these results point to the dermal GAG matrix as an important component in the regulation of the human hair follicle growth cycle, and to GAG-based hydrogels as potentially relevant modulators of this process both in vitro and in vivo.
糖胺聚糖 (GAGs) 和相关的蛋白聚糖在皮肤的稳态维持和再生过程(例如伤口修复)中具有重要功能。然而,人们对这些分子在毛囊周期调控中的作用知之甚少。在这里,我们报告说,在模拟真皮基质的特定 GAG 水凝胶中体外培养生长的人类毛囊强烈促进毛囊和毛囊上区域的细胞持续存活和高度增殖表型的维持。这种显著的效果与 WNT/β-连环蛋白信号靶标(CCDN1、AXIN2)的激活以及干细胞标记物(CK15、CD34)和参与休止期/生长期转换的生长因子(TGFβ2、FGF10)的表达有关。总的来说,这些结果表明真皮 GAG 基质是调节人类毛囊生长周期的重要组成部分,并且 GAG 水凝胶作为体外和体内该过程的潜在相关调节剂。