Platelet-Released Growth Factors and Platelet-Rich Fibrin Induce Expression of Factors Involved in Extracellular Matrix Organization in Human Keratinocytes

Andreas Bayer,Regine Gläser,Mersedeh Tohidnezhad,Bernard Wijaya,Daniel Drücke,Lena Möbus,Franziska Rademacher,Jürgen Harder,Meno Rodewald,Thomas Pufe

doi:10.3390/ijms21124404

Abstract

Platelet-released growth factor (PRGF) is a thrombocyte concentrate lysate which, like its clinically equivalent variations (e.g., Vivostat PRF® (platelet-rich fibrin)), is known to support the healing of chronic and hard-to-heal wounds. However, studies on the effect of PRGF on keratinocytes remain scarce. This study aims to identify genes in keratinocytes that are significantly influenced by PRGF. Therefore, we performed a whole transcriptome and gene ontology (GO) enrichment analysis of PRGF-stimulated human primary keratinocytes. This revealed an increased expression of genes involved in extracellular matrix (ECM) organization. Real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) analysis confirmed the PRGF-mediated induction of selected ECM-related factors such as transforming growth factor beta-induced protein, fibronectin 1, matrix metalloproteinase-9, transglutaminase 2, fermitin family member 1, collagen type I alpha 1 and collagen type XXII alpha 1. PRGF-induced expression of the above factors was influenced by blockade of the epidermal growth factor receptor (EGFR), a receptor playing a crucial role in wound healing. A differential induction of the investigated factors was also detected in skin explants exposed to PRGF and in experimentally generated in vivo wounds treated with Vivostat PRF®. Together, our study indicates that the induction of ECM-related factors may contribute to the beneficial wound-healing effects of PRGF-based formulations.

Highlights

Chronic or hard-to-heal wounds display a major problem for health care systems worldwide as they have an immense economic and social impact [1,2]
Gene ontology (GO) enrichment analysis revealed strong upregulation of factors involved in extracellular matrix (ECM) organization and cell morphology and motility (Figure 1)
Stimulation of human primary keratinocytes with platelet-released growth factors (PRGF) followed by whole transcriptome sequencing and analysis of gene ontology clustering revealed the upregulation of several factors involved in extracellular matrix (ECM) physiology, cellular interactions and angiogenesis

Summary

Introduction

Chronic or hard-to-heal wounds display a major problem for health care systems worldwide as they have an immense economic and social impact [1,2]. Their therapy is often difficult, lengthy and expensive [3,4,5,6]. We have shown that PRGF and Vivostat PRF® induced the expression of antimicrobial peptides [22,23,24] and influenced keratinocytes differentiation [25] and proliferation [26]. These data suggest a profound influence of PRGF on keratinocytes physiology

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