Role of processed peptides of the basement membrane component laminin in skin barrier function

层粘连蛋白在人类皮肤的基底膜结构和功能中起着重要作用。几种层粘连蛋白β链的C-末端LG模块可以通过蛋白水解进行修饰，产生LG 1 -3和分泌的LG 4 -5模块。我们的初步数据显示，来自层粘连蛋白LG 4链的合成肽具有有效的抗微生物活性，并且能够通过膜透化作用杀死细菌。此外，LG 4衍生肽促进角质形成细胞的迁移/增殖，并对单核细胞具有趋化活性。有趣的是，层粘连蛋白的表达可以在细菌感染后增加。基于这些数据，我们提出分泌的层粘连蛋白LG 4 -5衍生肽在生理条件下在皮肤中提供基础水平的保护，并且在组织损伤/皮肤创伤和/或细菌感染后诱导层粘连蛋白表达和分泌以及蛋白酶活性，这导致加工的LG 4 -5肽的水平增加。在该提案中，我们将在正常生理和感染条件下在人类皮肤以及受伤的皮肤中鉴定天然加工的层粘连蛋白LG 4 -5肽，并探索LG 4 -5衍生的加工肽在皮肤先天防御中的功能作用。这些数据应该表明来自层粘连蛋白LG 4 -5模块的加工肽是否在保护人类皮肤免受感染的皮肤屏障功能中发挥重要作用。

Laminins play a fundamental role in basement membrane architecture and function in human skin. The C-terminal LG modules of several laminin ý chains can be modified by proteolysis generating a LG1-3 and secreted LG4-5 module. Our preliminary data show that synthetic peptides derived from laminin ý3, ý4 and ý5 chain LG4 modules have effective antimicrobial activity and are able to kill bacteria by membrane permeabilization. In addition, LG4-derived peptides promote migration/proliferation of keratinocytes and have chemotactic activity for monocytes. Interestingly, expression of laminin can be increased after bacterial infection. Based on these data, we propose that secreted laminin LG4-5-derived peptides provide a basal level of protection in skin under physiological conditions and that after tissue damage/skin wounding and/or bacterial infection laminin expression and secretion is induced as well as protease activity which results in increased levels of processed LG4-5 peptides. In the proposal we will identify the naturally processed laminin LG4-5 peptides under normal physiological and infectious conditions in human skin as well as in wounded skin and explore the functional role of the LG4-5 derived processed peptides in skin innate defense. The data should indicate whether processed peptides from the laminin LG4-5 modules play an important role in skin barrier function protecting human skin against infection.