Platelet-Released Growth Factors Induce Genes Involved in Extracellular Matrix Formation in Human Fibroblasts.

Andreas Bayer,Bernard Wijaya,Jan-Tobias Weitkamp,Lena Möbus,Yusuke Kubo,Jürgen Harder,Mark Preuß,Regine Gläser,Meno Rodewald,Mersedeh Tohidnezhad,Peter Behrendt,Michael Singh,Franziska Rademacher

doi:10.3390/ijms221910536

Abstract

Platelet concentrate products are increasingly used in many medical disciplines due to their regenerative properties. As they contain a variety of chemokines, cytokines, and growth factors, they are used to support the healing of chronic or complicated wounds. To date, underlying cellular mechanisms have been insufficiently investigated. Therefore, we analyzed the influence of Platelet-Released Growth Factors (PRGF) on human dermal fibroblasts. Whole transcriptome sequencing and gene ontology (GO) enrichment analysis of PRGF-treated fibroblasts revealed an induction of several genes involved in the formation of the extracellular matrix (ECM). Real-time PCR analyses of PRGF-treated fibroblasts and skin explants confirmed the induction of ECM-related genes, in particular transforming growth factor beta-induced protein (TGFBI), fibronectin 1 (FN1), matrix metalloproteinase-9 (MMP-9), transglutaminase 2 (TGM2), fermitin family member 1 (FERMT1), collagen type I alpha 1 (COL1A1), a disintegrin and metalloproteinase 19 (ADAM19), serpin family E member 1 (SERPINE1) and lysyl oxidase-like 3 (LOXL3). The induction of these genes was time-dependent and in part influenced by the epidermal growth factor receptor (EGFR). Moreover, PRGF induced migration and proliferation of the fibroblasts. Taken together, the observed effects of PRGF on human fibroblasts may contribute to the underlying mechanisms that support the beneficial wound-healing effects of thrombocyte concentrate products.

Highlights

We have shown that the treatment of human keratinocytes with Platelet-released growth factors (PRGF) and Platelet-Rich Fibrin (PRF) leads to an induction of the antimicrobial peptides human beta-defensin-2 [5], hBD-3 [6] and psoriasin
To obtain an unbiased overview about the genes in fibroblasts that are regulated by unbiased overview about the genes in fibroblasts that are regulated by PRGF,Toa obtain wholean transcriptome analysis was performed with fibroblasts stimulated with
We have shown that PRGF induced several factors in primary keratinocytes that play a role in extracellular matrix (ECM) formation and we speculated that this might be human keratinocytes that play a role in ECM formation and we speculated that this might one reason for the beneficial wound healing properties of thrombocyte concentrate prodbe one reason for the beneficial wound healing properties of thrombocyte concentrate ucts [10]

Summary

Introduction

Platelet concentrate products, such as Platelet-Rich Fibrin (PRF) or Platelet-released growth factors (PRGF), are increasingly used worldwide in many areas of regenerative medicine [1] because they contain a multitude of growth factors, cytokines, and chemokines [2]. In the context of wound healing, it has been shown that 70% of chronic or complicated wounds heal or become smaller under the treatment of PRF [3,4]. The underlying mechanisms for these positive wound healing effects under treatment with platelet concentrate products remain poorly understood.

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Results

Conclusion