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@PHDTHESIS{Stein:1020931,
author = {Stein, Matthias},
othercontributors = {Pufe, Thomas and Conrads, Georg},
title = {{D}ie {R}olle von {N}rf2 bei der {R}egeneration und
{A}lterung der {H}aut unter {E}insatz von {PRGF}
({P}latelet-{R}eleased-{G}rowth {F}actors) in einem in-vitro
{H}autmodell},
school = {Rheinisch-Westfälische Technische Hochschule Aachen},
type = {Dissertation},
address = {Aachen},
publisher = {RWTH Aachen University},
reportid = {RWTH-2025-09339},
pages = {1 Online-Ressource : Illustrationen},
year = {2025},
note = {Veröffentlicht auf dem Publikationsserver der RWTH Aachen
University 2026; Dissertation, Rheinisch-Westfälische
Technische Hochschule Aachen, 2025},
abstract = {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.},
cin = {511001-5 ; 921210},
ddc = {610},
cid = {$I:(DE-82)511001-5_20140620$},
typ = {PUB:(DE-HGF)11},
doi = {10.18154/RWTH-2025-09339},
url = {https://publications.rwth-aachen.de/record/1020931},
}