Review
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World J Biol Chem. May 26, 2014; 5(2): 169-179
Published online May 26, 2014. doi: 10.4331/wjbc.v5.i2.169
Activated protein C: A regulator of human skin epidermal keratinocyte function
Kelly McKelvey, Christopher John Jackson, Meilang Xue
Kelly McKelvey, Christopher John Jackson, Meilang Xue, Sutton Arthritis Research Laboratory, Level 10, Kolling Institute, University of Sydney at Royal North Shore Hospital, NSW 2065, Australia
Author contributions: McKelvey K and Xue M contributed equally in writing the manuscript; Jackson CJ provided critique and comment on the manuscript.
Supported by Ulysses Club Arthritis Research Fellowship; and Henry Langley Arthritis Research Fellowship respectively, to McKelvey K and Xue M
Correspondence to: Dr. Meilang Xue, Sutton Arthritis Research Laboratory, Level 10, Kolling Institute, University of Sydney at Royal North Shore Hospital, St. Leonards, NSW 2065, Australia. meilang.xue@sydney.edu.au
Telephone: +61-2-99264816 Fax: +61-2-99266269
Received: October 23, 2013
Revised: January 20, 2014
Accepted: April 3, 2014
Published online: May 26, 2014
Abstract

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.

Keywords: Activated protein C, Endothelial protein C receptor, Protease-activated receptor, Keratinocyte, Proliferation, Junction protein, Barrier function

Core tip: The anti-inflammatory, barrier stabilisation and anti-apoptotic properties of APC make it an appealing treatment for skin conditions associated with inflammation, barrier disruption and keratinocyte dysfunction.