Cited by 97Wound Healing and TreatmentsDermatologic Treatments and ResearchBurn Injury Management and Outcomes

Scar Prevention and Enhanced Wound Healing Induced by Polydeoxyribonucleotide in a Rat Incisional Wound-Healing Model

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Jeong, Woonhyeok, Yang, Chae Eun, Roh, Tai Suk, Kim, Jun Hyung, Lee, Ju Hee, Lee, Won Jai·2017·International Journal of Molecular Sciences

Abstract

High-mobility group box protein-1 (HMGB-1) plays a central role in the inflammatory network, and uncontrolled chronic inflammation can lead to excessive scarring. The aim of this study was to evaluate the anti-inflammatory effects of polydeoxyribonucleotide (PDRN) on scar formation. Sprague-Dawley rats (n = 30) underwent dorsal excision of the skin, followed by skin repair. PDRN (8 mg/kg) was administered via intraperitoneal injection for three (PDRN-3 group, n = 8) or seven (PDRN-7 group, n = 8) days, and HMGB-1 was administered via intradermal injection in addition to PDRN treatment for three days (PDRN-3+HMGB-1 group; n = 6). The scar-reducing effects of PDRN were evaluated in the internal scar area and by inflammatory cell counts using histology and immunohistochemistry. Western blot, immunohistochemistry and immunofluorescence assays were performed to observe changes in type I and type III collagen and the expression of HMGB-1 and CD45. Treatment with PDRN significantly reduced the scar area, inflammatory cell infiltration and the number of CD45-positive cells. In addition, the increased expression of HMGB-1 observed in the sham group was significantly reduced after treatment with PDRN. Rats administered HMGB-1 in addition to PDRN exhibited scar areas with inflammatory cell infiltration similar to the sham group, and the collagen synthesis effects of PDRN were reversed. In summary, PDRN exerts anti-inflammatory and collagen synthesis effects via HMGB-1 suppression, preventing scar formation. Thus, we believe that the anti-inflammatory and collagen synthesis effects of PDRN resulted in faster wound healing and decreased scar formation.

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  • Upon enzymatic degradation, PDRN yields a pool of bioavailable nucleosides and nucleotides that can be rapidly reincorporated into cellular processes, promoting tissue regeneration and accelerating wound healing.

    “Upon enzymatic degradation, PDRN yields a pool of bioavailable nucleosides and nucleotides that can be rapidly reincorporated into cellular processes, thereby promoting tissue regeneration and accelerating wound healing [50,75,76,77].”

    From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [75]

    The Discussion (page not provided) reports faster wound healing after PDRN treatment and attributes it to reduced inflammation and increased collagen synthesis. The Introduction describes PDRN as a mixture of nucleotides, but our copy does not say that enzymatic degradation releases bioavailable nucleosides and nucleotides for rapid reincorporation into cellular processes. That proposed mechanism is not supported by this source. (LLM, conf=0.86)

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  1. [1]Oryan A. Alemzadeh E. Moshiri A. Biological properties and therapeutic activities of honey in wound healing: A narrative review and meta-analysis J. Tissue Viability 2016 25 98 118 10.1016/j.jtv.2015.12.002 26852154 · DOI
  2. [2]Wang J. Ding J. Jiao H. Honardoust D. Momtazi M. Shankowsky H.A. Tredget E.E. Human hypertrophic scar-like nude mouse model: Characterization of the molecular and cellular biology of the scar process Wound Repair Regen. 2011 19 274 285 10.1111/j.1524-475X.2011.00672.x 21362096 · DOI
  3. [3]Wang J.F. Hori K. Ding J. Huang Y. Kwan P. Ladak A. Tredget E.E. Toll-like receptors expressed by dermal fibroblasts contribute to hypertrophic scarring J. Cell Physiol. 2011 226 1265 1273 10.1002/jcp.22454 20945369 · DOI
  4. [4]Ogawa R. Keloid and hypertrophic scars are the result of chronic inflammation in the reticular dermis Int. J. Mol. Sci. 2017 18 606 10.3390/ijms18030606 28287424 PMC5372622 · DOI
  5. [5]Wulff B.C. Parent A.E. Meleski M.A. DiPietro L.A. Schrementi M.E. Wilgus T.A. Mast cells contribute to scar formation during fetal wound healing J. Investig. Dermatol. 2012 132 458 465 10.1038/jid.2011.324 21993557 PMC3258379 · DOI
  6. [8]Brown J.J. Bayat A. Genetic susceptibility to raised dermal scarring Br. J. Dermatol. 2009 161 8 18 10.1111/j.1365-2133.2009.09258.x 19508304 · DOI
  7. [9]Bran G.M. Goessler U.R. Hormann K. Riedel F. Sadick H. Keloids: Current concepts of pathogenesis (review) Int. J. Mol. Med. 2009 24 283 293 10.3892/ijmm_00000231 19639219 · DOI
  8. [10]Shih B. Garside E. McGrouther D.A. Bayat A. Molecular dissection of abnormal wound healing processes resulting in keloid disease Wound Repair Regen. 2010 18 139 153 10.1111/j.1524-475X.2009.00553.x 20002895 · DOI
  9. [11]Al-Attar A. Mess S. Thomassen J.M. Kauffman C.L. Davison S.P. Keloid pathogenesis and treatment Plast. Reconstr. Surg. 2006 117 286 300 10.1097/01.prs.0000195073.73580.46 16404281 · DOI
  10. [14]Yoshizaki A. Komura K. Iwata Y. Ogawa F. Hara T. Muroi E. Takenaka M. Shimizu K. Hasegawa M. Fujimoto M. Clinical significance of serum HMGB-1 and sRAGE levels in systemic sclerosis: Association with disease severity J. Clin. Immunol. 2009 29 180 189 10.1007/s10875-008-9252-x 18825489 · DOI
  11. [15]Algandaby M.M. Breikaa R.M. Eid B.G. Neamatallah T.A. Abdel-Naim A.B. Ashour O.M. Icariin protects against thioacetamide-induced liver fibrosis in rats: Implication of anti-angiogenic and anti-autophagic properties Pharmacol. Rep. 2017 69 616 624 10.1016/j.pharep.2017.02.016 28505603 · DOI
  12. [16]Bitto A. Polito F. Irrera N. D’Ascola A. Avenoso A. Nastasi G. Campo G. Micali A. Bagnato G. Minutoli L. Polydeoxyribonucleotide reduces cytokine production and the severity of collagen-induced arthritis by stimulation of adenosine A2A receptor Arthritis Rheum. 2011 63 3364 3371 10.1002/art.30538 21769841 · DOI · Paper page
  13. [17]Rork T.H. Wallace K.L. Kennedy D.P. Marshall M.A. Lankford A.R. Linden J. Adenosine A2A receptor activation reduces infarct size in the isolated, perfused mouse heart by inhibiting resident cardiac mast cell degranulation Am. J. Physiol. Heart Circ. Physiol. 2008 295 H1825 H1833 10.1152/ajpheart.495.2008 18757481 PMC2614589 · DOI
  14. [18]Bitto A. Oteri G. Pisano M. Polito F. Irrera N. Minutoli L. Squadrito F. Altavilla D. Adenosine receptor stimulation by polynucleotides (PDRN) reduces inflammation in experimental periodontitis J. Clin. Periodontol. 2013 40 26 32 10.1111/jcpe.12010 23033941 · DOI
  15. [19]Bitto A. Polito F. Altavilla D. Minutoli L. Migliorato A. Squadrito F. Polydeoxyribonucleotide (PDRN) restores blood flow in an experimental model of peripheral artery occlusive disease J. Vasc. Surg. 2008 48 1292 1300 10.1016/j.jvs.2008.06.041 18971038 · DOI
  16. [20]Bitto A. Galeano M. Squadrito F. Minutoli L. Polito F. Dye J.F. Clayton E.A. Calò M. Venuti F.S. Vaccaro M. Polydeoxyribonucleotide improves angiogenesis and wound healing in experimental thermal injury Crit. Care Med. 2008 36 1594 1602 10.1097/CCM.0b013e318170ab5c 18434887 · DOI · Paper page
  17. [21]Sini P. Denti A. Cattarini G. Daglio M. Tira M.E. Balduini C. Effect of polydeoxyribonucleotides on human fibroblasts in primary culture Cell Biochem. Funct. 1999 17 107 114 10.1002/(SICI)1099-0844(199906)17:2<107::AID-CBF815>3.0.CO;2-# 10377956 · DOI
  18. [22]Galeano M. Bitto A. Altavilla D. Minutoli L. Polito F. Calo M. Cascio P.L. d’Alcontres F.S. Squadrito F. Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse Wound Repair Regen. 2008 16 208 217 10.1111/j.1524-475X.2008.00361.x 18318806 · DOI
  19. [23]Chan E.S. Fernandez P. Cronstein B.N. Adenosine in inflammatory joint diseases Purinergic Signal. 2007 3 145 152 10.1007/s11302-006-9046-7 18404428 PMC2096754 · DOI
  20. [24]Altavilla D. Squadrito F. Polito F. Irrera N. Calo M. Lo Cascio P. Galeano M. Cava L.L. Minutoli L. Marini H. Activation of adenosine A2A receptors restores the altered cell-cycle machinery during impaired wound healing in genetically diabetic mice Surgery 2011 149 253 261 10.1016/j.surg.2010.04.024 20570301 · DOI
  21. [25]Walmsley G.G. Maan Z.N. Wong V.W. Duscher D. Hu M.S. Zielins E.R. Wearda T. Muhonen E. McArdle A. Tevlin R. Scarless wound healing: Chasing the holy grail Plast. Reconstr. Surg. 2015 135 907 917 10.1097/PRS.0000000000000972 25719706 · DOI
  22. [26]Szpaderska A.M. DiPietro L.A. Inflammation in surgical wound healing: Friend or foe? Surgery 2005 137 571 573 10.1016/j.surg.2005.01.006 15855932 · DOI · Paper page
  23. [27]Xue M. Jackson C.J. Extracellular matrix reorganization during wound healing and its impact on abnormal scarring Adv. Wound Care 2015 4 119 136 10.1089/wound.2013.0485 25785236 PMC4352699 · DOI · Paper page
  24. [28]Nakano A. Harada T. Morikawa S. Kato Y. Expression of leukocyte common antigen (CD45) on various human leukemia/lymphoma cell lines Acta. Pathol. Jpn. 1990 40 107 115 10.1111/j.1440-1827.1990.tb01549.x 2140233 · DOI · Paper page
  25. [29]Vaccari T. Beltrame M. Ferrari S. Bianchi M.E. Hmg4, a new member of the Hmg1/2 gene family Genomics 1998 49 247 252 10.1006/geno.1998.5214 9598312 · DOI
  26. [30]Andersson U. Wang H. Palmblad K. Aveberger A.C. Bloom O. Erlandsson-Harris H. Janson A. Kokkola R. Zhang M. Yang H. High mobility group 1 protein (HMG-1) stimulates proinflammatory cytokine synthesis in human monocytes J. Exp. Med. 2000 192 565 570 10.1084/jem.192.4.565 10952726 PMC2193240 · DOI
  27. [31]Lee D.E. Trowbridge R.M. Ayoub N.T. Agrawal D.K. High-mobility group box protein-1, matrix metalloproteinases, and vitamin D in keloids and hypertrophic scars Plast. Reconstr. Surg. Glob. Open 2015 3 e425 10.1097/GOX.0000000000000391 26180726 PMC4494495 · DOI
  28. [32]Dardenne A.D. Wulff B.C. Wilgus T.A. The alarmin HMGB-1 influences healing outcomes in fetal skin wounds Wound Repair Regen. 2013 21 282 291 10.1111/wrr.12028 23438257 PMC3594575 · DOI

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Authors
Jeong, W., Yang, C. E., Roh, T. S., Kim, J. H., Lee, J. H., & Lee, W. J.
Affiliations
  • Keimyung University Dongsan Medical Center (KR)
  • Severance Hospital (KR)
  • Department of Plastic and Reconstructive Surgery, School of Medicine & Institute for Medical Science, Keimyung University, Dongsan Medical Center, Daegu 41931, Korea
  • Yonsei University (KR)
Corresponding author
  • Lee, Ju Hee
  • Lee, Won Jai
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2017-08-03
Volume
18
Issue
8
Pages
1698
ISSN
1422-0067 (ISSN-L)
OpenAlex
W2743752524
Cited by
97
References
4
Citations by year
2026: 13 · 2025: 12 · 2024: 11 · 2023: 11 · 2022: 14 · 2021: 9 · 2020: 5 · 2019: 10 · 2018: 8 · 2017: 3
FWCI
6.77
Type
journal article
Language
en
Open access
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
Funders
National Research Foundation of Korea (NRF) grant (MEST; No. 2014051295, WJ Lee)
Topics
  • Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
  • Health Sciences › Medicine › Dermatology › Dermatologic Treatments and Research
  • Health Sciences › Medicine › Epidemiology › Burn Injury Management and Outcomes
Keywords
polydeoxyribonucleotide, scar prevention, wound healing, HMGB1, chronic inflammation, anti-inflammatory activity, collagen synthesis, type I collagen, type III collagen, inflammatory cell infiltration, CD45, excision wound
MeSH terms
Animals, Cicatrix, Disease Models, Animal, Male, Polydeoxyribonucleotides, Wound Healing, Wounds and Injuries, Rats, Sprague-Dawley, Collagen Type I, Collagen Type III, HMGB1 Protein, Rats

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