Activated protein C: A regulator of human skin epidermal keratinocyte function

• 作者: Christopher John Jackson Kelly McKelvey Meilang Xue
• 来源期刊: 世界生物化学杂志：英文版（电子版）
• 学科: 医学
• 关键词: ACTIVATED PROTEIN C Endothelial PROTEIN C RECEPTOR Protease-activated RECEPTOR KERATINOCYTE Proliferation Junction PROTEIN Barrier FUNCTION
• 年，卷（期）: 2014,（2）
• 页码范围: 169-179
• 页数: 11页
• 分类号: R241

摘要

Activated protein C(APC) is a physiological anticoagulant, derived from its precursor protein C(PC). Independent of its anticoagulation, APC possesses strong anti-inflammatory, anti-apoptotic and barrier protective properties which appear to be protective in a number of disorders including chronic wound healing. The epidermis is the outermost skin layer and provides the first line of defence against the external environment. Keratinocytes are the most predominant cells in the epidermis and play a critical role in maintaining epidermal barrier function. PC/APC and its receptor, endothelial protein C receptor(EPCR), once thought to be restricted to the endothelium, are abundantly expressed by skin epidermal keratinocytes. These cells respond to APC by upregulating proliferation, migration and matrix metalloproteinase-2 activity and inhibiting apoptosis/inflammation leading to a wound healing phenotype. APC also increases barrier function of keratinocyte monolayers by promoting the expression of tight junction proteins and re-distributing them to cell-cell contacts. These cytoprotective properties of APC are mediated through EPCR, protease-activated receptors, epidermal growth factor receptor or Tie2. Future preventive and therapeutic uses of APC in skin disorders associated with disruption of barrier function and inflammation look promising. This review will focus on APC’s function in skin epidermis/keratinocytes and its therapeutical potential in skin inflammatory conditions.