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%0 Thesis %A Stein, Matthias %T Die Rolle von Nrf2 bei der Regeneration und Alterung der Haut unter Einsatz von PRGF (Platelet-Released-Growth Factors) in einem in-vitro Hautmodell %I Rheinisch-Westfälische Technische Hochschule Aachen %V Dissertation %C Aachen %M RWTH-2025-09339 %P 1 Online-Ressource : Illustrationen %D 2025 %Z Veröffentlicht auf dem Publikationsserver der RWTH Aachen University 2026 %Z Dissertation, Rheinisch-Westfälische Technische Hochschule Aachen, 2025 %X 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. %F PUB:(DE-HGF)11 %9 Dissertation / PhD Thesis %R 10.18154/RWTH-2025-09339 %U https://publications.rwth-aachen.de/record/1020931