The Antimicrobial Peptide Human Beta-Defensin-3 Is Induced by Platelet-Released Growth Factors in Primary Keratinocytes

Abstract

Platelet-released growth factors (PRGF) and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF®)) contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3) is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting activities suggests that hBD-3 may play a crucial role in wound healing. Therefore, we analyzed the influence of PRGF on hBD-3 expression in human primary keratinocytes in vitro. In addition, we investigated the influence of Vivostat PRF on hBD-3 expression in artificially generated human skin wounds in vivo. PRGF treatment of primary keratinocytes induced a significant, concentration- and time-dependent increase in hBD-3 gene expression which was partially mediated by the epidermal growth factor receptor (EGFR). In line with these cell culture data, in vivo experiments revealed an enhanced hBD-3 expression in experimentally produced human wounds after the treatment with Vivostat PRF. Thus, the induction of hBD-3 may contribute to the beneficial effects of thrombocyte concentrate lysates in the treatment of chronic or infected wounds.

The Designer Antimicrobial Peptide A-hBD-2 Facilitates Skin Wound Healing by Stimulating Keratinocyte Migration and Proliferation

“…The mechanism of EGFR activation by A-hBD-2 remains unclear and requires further investigation. Previous studies have reported that EGFR activation could also induce hBDs production from keratinocytes [23]. Thus, it could be suggested that the close interaction between hBDs and EGFR has multiple benefits for wound healing.…”

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

“…Still, the underlying mechanism is analyzed insufficiently. Recently, 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.…”

Anti-Microbial Peptides and Their Speculative Role in Periodontitis

“…In the β-defensin subfamily only hBD -1, -2 and -3 are substantially expressed in the oral cavity [16,22]. hBD-3 along with the respective three mentioned above are markedly expressed in epithelial cells that encrust some tissues and organs, fundamentally skin [23]. In non-inflamed gingival tissues and gingival crevicular fluid, hBD-1 and hBD-2 have been expressed, with maximum levels at gingival margin [22].…”