Abstract
Platelet-released growth factors (PRGFs) or other thrombocyte concentrate products, e.g., Platelet-Rich Fibrin (PRF), have become efficient tools of regenerative medicine in many medical disciplines. In the context of wound healing, it has been demonstrated that treatment of chronic or complicated wounds with PRGF or PRF improves wound healing in the majority of treated patients. Nevertheless, the underlying cellular and molecular mechanism are still poorly understood. Therefore, we aimed to analyze if PRGF-treatment of human keratinocytes caused the induction of genes encoding paracrine factors associated with successful wound healing. The investigated genes were Semaphorin 7A (SEMA7A), Angiopoietin-like 4 (ANGPLT4), Fibroblast Growth Factor-2 (FGF-2), Interleukin-32 (IL-32), the CC-chemokine-ligand 20 (CCL20), the matrix-metalloproteinase-2 (MMP-2), the chemokine C-X-C motif chemokine ligand 10 (CXCL10) and the subunit B of the Platelet-Derived Growth Factor (PDGFB). We observed a significant gene induction of SEMA7A, ANGPLT4, FGF-2, IL-32, MMP-2 and PDGFB in human keratinocytes after PRGF treatment. The CCL20- and CXCL10 gene expressions were significantly inhibited by PRGF therapy. Signal transduction analyses revealed that the PRGF-mediated gene induction of SEMA7A, ANGPLT4, IL-32 and MMP-2 in human keratinocytes was transduced via the IL-6 receptor pathway. In contrast, EGF receptor signaling was not involved in the PRGF-mediated gene expression of analyzed genes in human keratinocytes. Additionally, treatment of ex vivo skin explants with PRGF confirmed a significant gene induction of SEMA7A, ANGPLT4, MMP-2 and PDGFB. Taken together, these results describe a new mechanism that could be responsible for the beneficial wound healing properties of PRGF or related thrombocytes concentrate products such as PRF.
Highlights
Chronic or complicated wounds still display a major problem for the individual patient concerned and the health care system in general [1–4]
We analyzed the influence of Platelet-released growth factors (PRGFs) on the gene expression of Semaphorin 7A (SEMA7A), Angiopoietin-like 4 (ANGPLT4), Fibroblast Growth Factor-2 (FGF-2), Interleukin-32 (IL-32), the CC-chemokine-ligand 20 (CCL20), the matrix-metalloproteinase-2 (MMP-2), the chemokine C-X-C motif chemokine ligand 10 (CXCL10) and the subunit B of the Platelet-Derived Growth Factor (PDFGB) in primary human keratinocytes
To investigate a possible influence on SEMA7A, MMP-2, ANGPLT4, Platelet-derived growth factor subunit B (PDGFB), IL-32, FGF-2, CXCL10 and CCL20 gene expression, keratinocytes were stimulated with different concentrations of PRGF (1:50, 1:20, 1:10) for 24 h
Summary
Chronic or complicated wounds still display a major problem for the individual patient concerned and the health care system in general [1–4]. As wound healing is a well-orchestrated and multicellular process [18,19], we asked if PRGF treatment of keratinocytes causes the induction of factors that may act in a paracrine way on other cells, such as fibroblasts, endothelial cells and macrophages, that promote the wound-healing process. In this context, we analyzed the influence of PRGF on the gene expression of Semaphorin 7A (SEMA7A), Angiopoietin-like 4 (ANGPLT4), Fibroblast Growth Factor-2 (FGF-2), Interleukin-32 (IL-32), the CC-chemokine-ligand 20 (CCL20), the matrix-metalloproteinase-2 (MMP-2), the chemokine C-X-C motif chemokine ligand 10 (CXCL10) and the subunit B of the Platelet-Derived Growth Factor (PDFGB) in primary human keratinocytes. We assessed the relevance of the Epidermalderived Growth Factor Receptor (EGFR) and the Interleukin-6 (IL-6) pathway for the PRGF-mediated induction of the analyzed genes
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