Tammi R, Ripellino J A, Margolis R U, Maibach H I, Tammi M
Department of Anatomy, University of Kuopio, Finland.
J Invest Dermatol. 1989 Mar;92(3):326-32. doi: 10.1111/1523-1747.ep12277125.
Retinoic acid (RA) has been shown to retard the differentiation of epidermal keratinocytes by several morphologic and biochemical criteria. In this study, the epidermal content and localization of hyaluronate (HA), as well as its synthesis and disappearance in human skin organ culture, were characterized to test the idea that some of the RA influences on epidermal differentiation are associated with keratinocyte HA metabolism. RA stimulated the incorporation of 3H-glucosamine into HA by up to 60% at concentrations between 50 nM and 5 microM, while pulse-chase experiments revealed little change in its disappearance rate from epidermis. After 5 d in culture, the chemically quantified HA was more than doubled in the treated epidermis. The accumulation of HA was substantiated by light and electron microscopy with a specific probe prepared from the HA binding region of cartilage proteoglycan. The staining was particularly enhanced between the upper spinous cell layers, where the terminal differentiation into corneocytes normally takes place. A patchy, discontinuous staining was also seen in stratum granulosum and corneum layers, which are not stained at all in control cultures. The present study demonstrates that RA leads to an accumulation of HA in the superficial layers of epidermis by stimulating its synthesis in keratinocytes. This may account for the delay in terminal differentiation, and the weakened cohesion of the keratinocytes previously observed both in vivo and vitro.
维甲酸（RA）已通过多种形态学和生化标准显示出可延缓表皮角质形成细胞的分化。在本研究中，对透明质酸（HA）在人皮肤器官培养中的表皮含量和定位及其合成与消失情况进行了表征，以检验RA对表皮分化的某些影响与角质形成细胞HA代谢相关这一观点。RA在50 nM至5 μM的浓度下可使3H-葡萄糖胺掺入HA的量增加高达60%，而脉冲追踪实验显示其从表皮消失的速率变化不大。培养5天后，经化学定量的HA在处理后的表皮中增加了一倍多。用从软骨蛋白聚糖的HA结合区域制备的特异性探针进行光镜和电镜观察证实了HA的积累。在上棘细胞层之间染色特别增强，正常情况下角质形成细胞在此处发生终末分化。在颗粒层和角质层中也可见到斑片状、不连续的染色，而在对照培养物中这些层根本不染色。本研究表明，RA通过刺激角质形成细胞中HA的合成导致其在表皮表层积累。这可能解释了之前在体内和体外观察到的终末分化延迟以及角质形成细胞黏附力减弱的现象。
