Maytin Edward V, Chung Helen H, Seetharaman V Mani
Biomedical Engineering, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Am J Pathol. 2004 Oct;165(4):1331-41. doi: 10.1016/S0002-9440(10)63391-3.
Hyaluronan (hyaluronic acid, HA) is a glycosaminoglycan in the extracellular matrix of tissues that plays a role in cellular migration, proliferation and differentiation. Injury to the stratum corneum elicits an epidermal hyperproliferative response, a pathogenic feature in many cutaneous diseases including eczema and psoriasis. Because HA is abundant in the matrix between keratinocytes, we asked whether the presence of HA is required for epidermal hyperplasia to occur in response to barrier injury. Disruption of the stratum corneum, by acetone application on the skin of hairless mice, led to a marked accumulation of HA in the matrix between epidermal basal and spinous keratinocytes, and also within keratinocytes of the upper epidermis. To test whether HA may have a functional role in epidermal hyperplasia, we used Streptomyces hyaluronidase (StrepH), delivered topically, to degrade epidermal HA and blunt the accumulation of epidermal HA after acetone. StrepH signficantly reduced epidermal HA levels, and also significantly inhibited the development of epidermal hyperplasia. This reduction in epidermal thickness was not attributable to any decrease in keratinocyte proliferation, but rather to an apparent acceleration in terminal differentiation (ie, increased keratin 10 and filaggrin expression). Overall, the data show that HA is a significant participant in the epidermal response to barrier injury.
透明质酸（又称玻尿酸，HA）是一种存在于组织细胞外基质中的糖胺聚糖，在细胞迁移、增殖和分化过程中发挥作用。角质层损伤会引发表皮过度增殖反应，这是包括湿疹和牛皮癣在内的许多皮肤疾病的一个致病特征。由于透明质酸在角质形成细胞之间的基质中含量丰富，我们不禁要问，屏障损伤引发的表皮增生是否需要透明质酸的存在。通过在无毛小鼠皮肤上涂抹丙酮来破坏角质层，结果导致表皮基底细胞和棘层角质形成细胞之间的基质以及上表皮角质形成细胞内的透明质酸显著积聚。为了测试透明质酸在表皮增生中是否具有功能性作用，我们局部应用链霉菌透明质酸酶（StrepH）来降解表皮透明质酸，并抑制丙酮处理后表皮透明质酸的积聚。StrepH显著降低了表皮透明质酸水平，同时也显著抑制了表皮增生的发展。表皮厚度的这种降低并非归因于角质形成细胞增殖的任何减少，而是明显归因于终末分化的加速（即角蛋白10和丝聚蛋白表达增加）。总体而言，数据表明透明质酸是表皮对屏障损伤反应的重要参与者。
