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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},
}