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Cited by 45Wound Healing and TreatmentsDermatologic Treatments and ResearchPeriodontal Regeneration and Treatments

Polydeoxyribonucleotide exerts opposing effects on ERK activity in human skin keratinocytes and fibroblasts

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Shin, Sun Mee, Baek, Eun Joo, Kim, Kwang Ho, Kim, Kwang Joong, Park, Eun Joo·2023·Molecular Medicine Reports
DOI 10.3892/mmr.2023.13035PMC PMC10308489
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Abstract

Polydeoxyribonucleotide (PDRN) is a mixture of deoxyribonucleotides. It serves as an anti‑inflammatory and tissue‑regenerating agent. The mitogen‑activated protein kinase pathway modulates cell growth and collagen accumulation. It also regulates inflammation by suppressing the expression of proinflammatory cytokines. In the present study, it was attempted to elucidate the molecular mechanism of PDRN in skin healing by confirming the effects of PDRN treatment on skin keratinocytes and fibroblasts, and by assessing the levels of collagen and inflammatory cytokines regulated by the extracellular signal‑regulated kinase (ERK) pathway. The potential effects of PDRN on skin regeneration were investigated. Fibroblast and keratinocyte proliferation and migration were analyzed using the water‑soluble tetrazolium‑8 and wound healing assays. The upregulation of collagen synthesis by PDRN‑induced ERK activation was analyzed in fibroblasts with or without an ERK inhibitor. Inflammatory cytokine expression levels in keratinocytes were determined using reverse transcription‑quantitative polymerase chain reaction. PDRN promoted the proliferation and migration of keratinocytes and fibroblasts. However, PDRN‑induced ERK phosphorylation differed between keratinocytes and fibroblasts; PDRN increased ERK phosphorylation and collagen accumulation in fibroblasts, while it inhibited matrix metalloproteinase expression. By contrast, PDRN inhibited ERK phosphorylation in keratinocytes, and it decreased inflammatory cytokine expression levels. PDRN affects skin cell proliferation and migration, and collagen and inflammatory cytokine expression levels via ERK signaling. Overall, PDRN exerts a positive effect on skin regeneration, but the mechanism by which it promotes skin regeneration varies among different skin cell types.

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  • No standardized criteria have been established to delineate molecular weight thresholds that clearly distinguish PN from PDRN.

    “To date, no standardized criteria have been established to delineate molecular weight thresholds that clearly distinguish PN from PDRN, despite considerable variation among previously proposed classifications [11,20,77,143].”

    From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [20]

    The Discussion gives a molecular-weight range for PDRN (50–1,500 kDa), but does not compare PDRN with PN or discuss whether standardized thresholds distinguish them. Searches for PN/PDRN classification and molecular-weight criteria found no passage addressing that claim. (LLM, conf=0.74)

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  • Stringent isolation and purification processes are necessary for the clinical application of bioactive nucleic acids to ensure high purity, sterility, and product consistency.

    “The clinical application of bioactive nucleic acids necessitates stringent isolation and purification processes to ensure high purity, sterility, and product consistency [20,159].”

    From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [20]

    The Introduction describes PDRN’s biological uses, and Materials and methods describes isolating RNA for an assay and treating cells with a commercial PDRN product. Neither section addresses isolation or purification requirements for clinical products, or requirements for purity, sterility, and consistency (searched: purification, clinical quality, and product consistency). (LLM, conf=0.76)

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Cited by

Sorted by citations

Authors
Shin, S. M., Baek, E. J., Kim, K. H., Kim, K. J., & Park, E. J.
Affiliations
  • Hallym University Medical Center (KR)
  • Hallym University Sacred Heart Hospital (KR)
Corresponding author
Park, Eun Joo
ORCID
Venue
Molecular Medicine Reports
Publisher
Spandidos Publications
Published
2023-06-20
Volume
28
Issue
2
ISSN
  • 1791-2997 (ISSN-L)
  • 1791-3004
DOI
10.3892/mmr.2023.13035
PMC
PMC10308489
OpenAlex
W4381433115
Cited by
45
References
4
Citations by year
2026: 20 · 2025: 17 · 2024: 7 · 2023: 1
FWCI
4.95
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Molecular Medicine Reports (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Research Foundation
  • Hallym University
  • National Research Foundation of Korea (2019R1G1A100658813)
Topics
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
  • Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
Keywords
polydeoxyribonucleotide, ERK signaling, skin regeneration, keratinocytes, fibroblasts, collagen synthesis, matrix metalloproteinases, inflammatory cytokines, cell proliferation, cell migration, wound healing, anti-inflammatory activity
MeSH terms
Collagen, Fibroblasts, Humans, Phosphorylation, Polydeoxyribonucleotides, Skin, Keratinocytes, Cytokines, Extracellular Signal-Regulated MAP Kinases

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