Orchestrated control of multiple overlapping and sequential processes is required for the maintenance of epidermal homeostasis and the response to and recovery from a variety of skin insults. Previous studies indicate that membrane-associated serine protease matriptase and prostasin play essential roles in epidermal development, differentiation, and barrier formation. The control of proteolysis is a highly regulated process, which depends not only on gene expression but also on zymogen activation and the balance between protease and protease inhibitor. Subcellular localization can affect the accessibility of protease inhibitors to proteases and, thus, also represents an integral component of the control of proteolysis. To understand how membrane-associated proteolysis is regulated in human skin, these key aspects of matriptase and prostasin were determined in normal and injured human skin by immunohistochemistry. This staining shows that matriptase is expressed predominantly in the zymogen form at the periphery of basal and spinous keratinocytes, and prostasin appears to be constitutively activated at high levels in polarized organelle-like structures of the granular keratinocytes in the adjacent quiescent skin. The membrane-associated proteolysis appears to be elevated via an increase in matriptase zymogen activation and prostasin protein expression in areas of skin recovering from epidermal insults. There was no noticeable change observed in other regulatory aspects, including the expression and tissue distribution of their cognate inhibitors HAI-1 and HAI-2. This study reveals that the membrane-associated proteolysis may be a critical epidermal mechanism involved in responding to, and recovering from, damage to human skin.

为了维持表皮稳态以及对各种皮肤损伤的反应和从中恢复，需要对多个重叠和顺序过程进行协调控制。先前的研究表明，膜相关的丝氨酸蛋白酶Matriptase和前列腺素在表皮发育，分化和屏障形成中起重要作用。蛋白质水解的控制是高度受控的过程，其不仅取决于基因表达，而且取决于酶原的活化以及蛋白酶和蛋白酶抑制剂之间的平衡。亚细胞定位可影响蛋白酶抑制剂对蛋白酶的可及性，因此也代表了蛋白水解控制的组成部分。要了解人类皮肤中膜相关蛋白水解的调控方式，通过免疫组织化学法测定了正常和受伤的人皮肤中脂蛋白酶和前列腺素的这些关键方面。该染色表明，脂蛋白磷酸酶主要以酶原形式在基底和棘突角质形成细胞的外围表达，并且前列腺素似乎在相邻的静止皮肤的粒状角质形成细胞的极化细胞器样结构中被高水平组成性活化。膜相关的蛋白水解作用似乎是通过在从表皮损伤中恢复的皮肤区域中的过氧化氢酶酶原激活和前列腺素蛋白表达的增加而提高的。在其他调控方面，包括其同源抑制剂HAI-1和HAI-2的表达和组织分布，未见明显变化。