EPCR in Wound Healing: Mechanisms of Action and Therapeutic Potential

TL;DR

This paper explores how the EPCR protein helps wounds heal by managing coagulation, inflammation, and tissue repair, and suggests it could be used for new therapies.

Contribution

The paper highlights EPCR's novel role in wound healing phases and its potential as a therapeutic target and biomarker.

Findings

EPCR supports wound healing by enhancing anticoagulation during haemostasis and modulating inflammation.

EPCR promotes tissue repair by aiding cell proliferation and regulating fibroblast activity via the TGF-β1/Smad3 pathway.

Future therapies may use EPCR-based strategies, including targeted delivery and personalized treatment approaches.

Abstract

The endothelial protein C receptor (EPCR) is an important component of the protein C (PC) system, recognised for its diverse roles in blood coagulation, inflammation, and stem cell regulation. Wound healing is a complex physiological process that can be divided into four distinct but overlapping phases: haemostasis, inflammation, proliferation and remodelling. Recently, EPCR has emerged as a key regulator in wound repair and regeneration. During haemostasis, EPCR enhances the conversion of PC to its activated form (APC) to optimise local and systemic anticoagulation. In the inflammatory phase, EPCR modulates immune cell activity, inhibits inflammatory factors, and maintains tissue barrier integrity. As the process transitions to the proliferative phase, EPCR promotes endothelial and epithelial cell proliferation, migration, neovascularisation and re-epithelization, and mediates the expression of matrix metalloproteinases to facilitate tissue reconstruction. Finally, during the remodelling phase, EPCR exerts a potential antifibrotic effect by regulating fibroblast activation and collagen deposition via the Transforming growth factor (TGF)-β1/Smad3 pathway, ensuring functional repair. While therapeutic potential has been shown in animal models, translating EPCR-mediated therapies to clinical application faces many challenges, including wound heterogeneity, dosage control, targeted delivery, and potential bleeding risks. Studies have shown that local drug delivery strategies, non-anticoagulant APC variants, and individualised treatment based on EPCR expression will be the key directions for future development. Additionally, EPCR may serve as a potential biomarker for assessing wound severity and guiding personalised interventions.

Figures