32 Stein, Matthias Pufe, Thomas Conrads, Georg 511001-5 ; 921210 RWTH Aachen University Aachen German 1 Online-Ressource : Illustrationen Biostimulation with Platelet-Released Growth Factors (PRGFs) offers a growth factor rich therapeutic approach for the treatment and support of wound healing. The transcription factor NRF2 protects cells from oxidative stress, regulates the expression of antioxidant enzymes, and co-regulates inflammatory cell conditions through NF-κB inhibition. The influence of PRGF on the NRF2-ARE system in primary human keratinocytes, as well as its impact on NF-κB regulation in an NRF2-dependent manner, has not yet been investigated. Cell stimulation was characterized using proliferation and viability assays, while differentiation was examined using a dispase dissociation assay. In this study, the effect of PRGFs on the NRF2-ARE and NF-κB systems in keratinocytes was investigated by mono-luciferase assays. Additionally, gene expression analyses and Western blotting were performed to evaluate NRF2 target genes and proteins. These were complemented by functional ELISAs. The NRF2-dependency of the treatment was examined by using the NRF2 inhibitor ML-385. At the gene expression and protein levels, PRGF treatment showed an inductive effect on HO-1 and NQO1. Moreover, a NF-κBinhibitory effect of PRGF on keratinocytes was demonstrated in an inflammation model. Functionally, PRGF-NRF2 activation influenced the release of IL-1β, IL-6, IL-4, IL-10, and TNF-α. Additionally, it was shown that keratinocytes pretreated with PRGF and sulforaphane exhibited resilience against pro-inflammatory stressors. The antimicrobial peptides HBD-2, HBD-3 and LL-37 were also detected in the supernatants of PRGF treated cells. Following the presented results, previously published studies on the positive effect of PRP/PRGF on the NRF2-ARE system in bone, tendon, and cartilage cells can be extended to include human, primary keratinocytes. Additionally, preliminary evidence of NRF2-dependent PRGF-induced AMP regulation has been observed. Further characterization and investigation of PRGF's effects on NRF2, along with its promising anti-inflammatory and AMP-regulating effects, suggest that additional (clinical) studies for evaluation as a therapeutic approach are warranted. Veröffentlicht auf dem Publikationsserver der RWTH Aachen University 2026 ; Dissertation, Rheinisch-Westfälische Technische Hochschule Aachen, 2025 ; 2, ; PUB:(DE-HGF)11, ; Dissertation / PhD Thesis Dissertation Rheinisch-Westfälische Technische Hochschule Aachen 2025 2025 RWTH-2025-09339 2025 https://publications.rwth-aachen.de/record/1020931