Nauroy Pauline, Nyström Alexander
Department of Dermatology, Medical Center - University of Freiburg, Hauptstrasse 7, 79104 Freiburg, Germany.
Matrix Biol Plus. 2019 Nov 21;6-7:100019. doi: 10.1016/j.mbplus.2019.100019. eCollection 2020 May.
As the outermost layer of the skin, the epidermis is playing a major role in organism homeostasis providing the first barrier against external aggressions. Although considered as an extracellular matrix (ECM)-poor subtissue, the epidermal microenvironment is a key regulator of skin homeostasis and functionality. Among the proteins essential for upholding the epidermal microenvironment are the members of the kallikrein (KLK) family composed of 15 secreted serine proteases. Most of the members of these epithelial-specific proteins are present in skin and regulate skin desquamation and inflammation. However, although epidermal products, the consequences of KLK activities are not confined to the epidermis but widespread in the skin. In this review starting with the location and proteolytic activation cascade of KLKs, we present KLKs involvement in skin homeostasis, regeneration and pathology. KLKs have a large variety of substrates including ECM proteins, and evidence suggests that they are involved in the different steps of skin wound healing as discussed here. KLKs are also used as prognosis/diagnosis markers for many cancer types and we are focusing later on KLKs in cutaneous cancers, although their pathogenicity remains to be fully elucidated. Dysregulation of the KLK cascade is directly responsible for skin diseases with heavy inflammatory aspects, highlighting their involvement in skin immune homeostasis. Future studies will be needed to support the therapeutic potential of adjusting KLK activities for treatment of inflammatory skin diseases and wound healing pathologies.
作为皮肤的最外层，表皮在机体稳态中发挥着重要作用，为抵御外部侵害提供第一道屏障。尽管表皮被认为是一种细胞外基质（ECM）含量低的亚组织，但表皮微环境却是皮肤稳态和功能的关键调节因子。维持表皮微环境所必需的蛋白质中，有激肽释放酶（KLK）家族的成员，该家族由15种分泌型丝氨酸蛋白酶组成。这些上皮特异性蛋白质的大多数成员存在于皮肤中，调节皮肤脱屑和炎症。然而，尽管是表皮产物，但KLK活性的影响并不局限于表皮，而是在皮肤中广泛存在。在这篇综述中，我们从KLK的定位和蛋白水解激活级联反应入手，介绍KLK在皮肤稳态、再生和病理过程中的作用。KLK有多种底物，包括ECM蛋白，有证据表明它们参与了皮肤伤口愈合的不同阶段，如下文所述。KLK也被用作多种癌症类型的预后/诊断标志物，我们稍后将重点关注皮肤癌中的KLK，尽管它们的致病性仍有待充分阐明。KLK级联反应的失调直接导致具有严重炎症特征的皮肤疾病，突出了它们在皮肤免疫稳态中的作用。未来的研究需要支持调节KLK活性在治疗炎症性皮肤病和伤口愈合病理方面的治疗潜力。
