2nd Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Exp Dermatol. 2009 Dec;18(12):1028-35. doi: 10.1111/j.1600-0625.2009.00889.x.
Extrinsic skin ageing or 'photoageing', as opposed to intrinsic skin ageing, is the result of exposure to external factors, mainly ultraviolet irradiation. Glycosaminoglycans (GAG) and particularly hyaluronic acid (HA) are major components of the cutaneous extracellular matrix involved in tissue repair. However, their involvement in extrinsic skin ageing remains elusive. In this study, we investigated the expression of HA and its metabolizing enzymes in photoexposed and photoprotected human skin tissue specimens, obtained from the same patient. Total GAG were isolated, characterized using specific GAG-degrading enzymes and separated by electrophoresis on cellulose acetate membranes and polyacrylamide gels. Quantitation of HA in total GAG was performed using ELISA. Gene expression of hyaluronan synthases (HAS), hyaluronidases (HYAL) and HA receptors CD44 and receptor for HA-mediated motility (RHAMM) was assessed by RT-PCR. We detected a significant increase in the expression of HA, of lower molecular mass, in photoexposed skin as compared with photoprotected skin. This increase was associated with a significant decrease in the expression of HAS1 and an increase in the expression of HYAL1-3. Furthermore, the expression of HA receptors CD44 and RHAMM was significantly downregulated in photoexposed as compared with photoprotected skin. These findings indicate that extrinsic skin ageing is characterized by distinct homoeostasis of HA. The elucidation of the role of HA homoeostasis in extrinsic skin ageing may offer an additional approach in handling cutaneous ageing.
外在皮肤老化或“光老化”与内在皮肤老化相反，是暴露于外部因素（主要是紫外线照射）的结果。糖胺聚糖（GAG），特别是透明质酸（HA）是参与组织修复的皮肤细胞外基质的主要成分。然而，它们在外部皮肤老化中的作用仍不清楚。在这项研究中，我们研究了 HA 及其代谢酶在来自同一患者的光暴露和光保护的人皮肤组织标本中的表达。分离总 GAG，使用特定的 GAG 降解酶对其进行特征分析，并通过醋酸纤维素膜和聚丙烯酰胺凝胶电泳进行分离。使用 ELISA 定量测定总 GAG 中的 HA。通过 RT-PCR 评估透明质酸合成酶（HAS）、透明质酸酶（HYAL）和 HA 受体 CD44 和 HA 介导的运动受体（RHAMM）的基因表达。与光保护皮肤相比，我们在光暴露皮肤中检测到 HA 的表达增加，且分子量较低。这种增加与 HAS1 表达的显著降低和 HYAL1-3 表达的增加有关。此外，与光保护皮肤相比，HA 受体 CD44 和 RHAMM 在光暴露皮肤中的表达明显下调。这些发现表明，外在皮肤老化的特征是 HA 的明显动态平衡。阐明 HA 动态平衡在外在皮肤老化中的作用可能为处理皮肤老化提供另一种方法。
