PDRN, a Bioactive Natural Compound, Ameliorates Imiquimod-Induced Psoriasis through NF-κB Pathway Inhibition and Wnt/β-Catenin Signaling Modulation
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Nuclear factor-κB (NF-κB) plays a central role in psoriasis and canonical Wnt/β-catenin pathway blunts the immune-mediated inflammatory cascade in psoriasis. Adenosine A2A receptor activation blocks NF-κB and boosts the Wnt/β-catenin signaling. PDRN (Polydeoxyribonucleotide) is a biologic agonist of the A2A receptor and its effects were studied in an experimental model of psoriasis. Psoriasis-like lesions were induced by a daily application of imiquimod (IMQ) on the shaved back skin of mice for 7 days. Animals were randomly assigned to the following groups: Sham psoriasis challenged with Vaseline; IMQ animals challenged with imiquimod; and IMQ animals treated with PDRN (8 mg/kg/ip). An additional arm of IMQ animals was treated with PDRN plus istradefylline (KW6002; 25 mg/kg/ip) as an A2A antagonist. PDRN restored a normal skin architecture, whereas istradefylline abrogated PDRN positive effects, thus pointing out the mechanistic role of the A2A receptor. PDRN decreased pro-inflammatory cytokines, prompted Wnt signaling, reduced IL-2 and increased IL-10. PDRN also reverted the LPS repressed Wnt-1/β-catenin in human keratinocytes and these effects were abolished by ZM241385, an A2A receptor antagonist. Finally, PDRN reduced CD3+ cells in superficial psoriatic dermis. PDRN anti-psoriasis potential may be linked to a “dual mode” of action: NF-κB inhibition and Wnt/β-catenin stimulation.
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In an imiquimod-induced murine model of psoriasis, PDRN mediates anti-inflammatory effects through activation of the adenosine A2A receptor.
“Moreover, in an imiquimod-induced murine model of psoriasis—an archetypal chronic inflammatory skin disease—PDRN mediates anti-inflammatory effects through activation of the adenosine A2A receptor [128].”
From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [128]
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Cites
Wnt/β-Catenin Signaling in Development and Disease
Clevers, H. (2006) · Cell · doi:10.1016/j.cell.2006.10.018 · Cited by 5,568 · see citing works
The Wnt Signaling Pathway in Development and Disease
Logan, C. Y., & Nusse, R. (2004) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.20.010403.113126 · Cited by 5,325 · see citing works
Animal research: Reporting <i>in vivo</i> experiments: The ARRIVE guidelines
Kilkenny, C., Browne, W., Cuthill, I. C., Emerson, M., & Altman, D. G. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00872.x · Cited by 3,625 · see citing works
Nestle, F. O., Kaplan, D. H., & Barker, J. (2009) · New England Journal of Medicine · doi:10.1056/nejmra0804595 · Cited by 2,788 · see citing works
Animal Research: Reporting <i>in vivo</i> Experiments—The ARRIVE Guidelines
Kilkenny, C., Browne, W., Cuthill, I. C., Emerson, M., & Altman, D. G. (2011) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2010.220 · Cited by 2,012 · see citing works
Wnt signal transduction pathways
Komiya, Y., & Habas, R. (2008) · Organogenesis · doi:10.4161/org.4.2.5851 · Cited by 1,528 · see citing works
Adenosine receptors: therapeutic aspects for inflammatory and immune diseases
Haskó, G., Linden, J. M., Cronstein, B. N., & Pacher, P. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2638 · Cited by 1,224 · see citing works
Arican, O., Aral, M., Sasmaz, S., & Ciragil, P. (2005) · Mediators of Inflammation · doi:10.1155/mi.2005.273 · Cited by 805 · see citing works
Pathogenesis of psoriasis and development of treatment
Ogawa, E., Sato, Y., Minagawa, A., & Okuyama, R. (2017) · The Journal of Dermatology · doi:10.1111/1346-8138.14139 · Cited by 464 · see citing works
Immunopathogenic mechanisms in psoriasis
Gudjonsson, J. E., Johnston, A. W. B., Sigmundsdóttir, H., & Valdimarsson, H. (2003) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2004.02310.x · Cited by 398 · see citing works
Pharmacological Activity and Clinical Use of PDRN
Squadrito, F., Bitto, A., Irrera, N., Pizzino, G., Pallio, G., Minutoli, L., & Altavilla, D. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00224 · Cited by 215 · see citing works
Self-citationMuch Ado about Adenosine: Adenosine Synthesis and Function in Regulatory T Cell Biology
Ernst, P. B., Garrison, J. C., & Thompson, L. F. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1000108 · Cited by 201 · see citing works
Schön, M. P., Schön, M., & Klotz, K. (2006) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700286 · Cited by 164 · see citing works
Irrera, N., Vaccaro, M., Bitto, A., Pallio, G., Pizzino, G., Lentini, M., Arcoraci, V., Minutoli, L., Scuruchi, M., Cutroneo, G., et al. (2017) · Clinical Science · doi:10.1042/cs20160645 · Cited by 147 · see citing works
Self-citationNewby, A. C., Holmquist, C. A., ILLINGWORTH, J. A., & Pearson, J. D. (1983) · Biochemical Journal · doi:10.1042/bj2140317 · Cited by 108 · see citing works
Bitto, A., Polito, F., Irrera, N., D'Ascola, A., Avenoso, A., Nastasi, G., Campo, G. M., Micali, A., Bagnato, G., Minutoli, L., et al. (2011) · Arthritis & Rheumatism · doi:10.1002/art.30538 · Cited by 105 · see citing works
Self-citationMediero, A., Perez‐Aso, M., & Cronstein, B. N. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12227 · Cited by 93 · see citing works
Role of Wnt5a in the Pathogenesis of Inflammatory Diseases
Pashirzad, M., Shafiee, M., Rahmani, F., Behnam‐Rassouli, R., Hoseinkhani, F., Ryzhikov, M., Binabaj, M. M., Parizadeh, M. R., Avan, A., & Hassanian, S. M. (2016) · Journal of Cellular Physiology · doi:10.1002/jcp.25687 · Cited by 91 · see citing works
Irrera, N., Arcoraci, V., Mannino, F., Vermiglio, G., Pallio, G., Minutoli, L., Bagnato, G., Anastasi, G., Mazzon, E., Bramanti, P., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00506 · Cited by 74 · see citing works
Self-citationAltavilla, D., Squadrito, F., Polito, F., Irrera, N., Calò, M., Cascio, P. L., Galeano, M., Cava, L. L., Minutoli, L., & Marini, H. R. (2010) · Surgery · doi:10.1016/j.surg.2010.04.024 · Cited by 71 · see citing works
Self-citationInterleukin-23 and interleukin-17: Importance in pathogenesis and therapy of psoriasis
Mudigonda, P., Mudigonda, T. V., Feneran, A. N., Alamdari, H. S., Sandoval, L. F., & Feldman, S. R. (2012) · Dermatology Online Journal · doi:10.5070/d33n39n8xm · Cited by 70 · see citing works
Bitto, A., Oteri, G., Pisano, M., Polito, F., Irrera, N., Minutoli, L., Squadrito, F., & Altavilla, D. (2012) · Journal Of Clinical Periodontology · doi:10.1111/jcpe.12010 · Cited by 67 · see citing works
Self-citationLi, Y., Zhang, G., Chen, M., Tong, M., Zhao, M., Tang, F., Xiao, R., & Wen, H. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.10.062 · Cited by 54 · see citing works
Pallio, G., Bitto, A., Pizzino, G., Galfo, F., Irrera, N., Squadrito, F., Squadrito, G., Pallio, S., Anastasi, G., Cutroneo, G., et al. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00273 · Cited by 46 · see citing works
Self-citationShaikh, G., Zhang, J., Pérez‐Aso, M., Mediero, A., & Cronstein, B. N. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13615 · Cited by 40 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Pathogenesis, multi-omics research, and clinical treatment of psoriasis
Yu, J., Zhao, Q., Wang, X., Zhou, H., Hu, J. Y., Gu, L., Hu, Y., Zeng, F., Zhao, F., Yue, C., et al. (2022) · Journal of Autoimmunity · doi:10.1016/j.jaut.2022.102916 · Cited by 111 · see citing works
Transcriptome-Wide m6A Methylation in Skin Lesions From Patients With Psoriasis Vulgaris
Wang, Y., & Jin, H. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.591629 · Cited by 58 · see citing works
Picciolo, G., Mannino, F., Irrera, N., Altavilla, D., Minutoli, L., Vaccaro, M., Arcoraci, V., Squadrito, V., Picciolo, G., Squadrito, F., et al. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111538 · Cited by 49 · see citing works
Self-citationAntonuccio, P., Micali, A. G., Romeo, C., Freni, J., Vermiglio, G., Puzzolo, D., Squadrito, F., Irrera, N., Marini, H. R., Rana, R. A., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031319 · Cited by 43 · see citing works
Self-citationWnt Signaling Pathways: From Inflammation to Non-Melanoma Skin Cancers
Bartolomeo, L. D., Vaccaro, F., Irrera, N., Borgia, F., Pomi, F. L., Squadrito, F., & Vaccaro, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021575 · Cited by 34 · see citing works
Self-citationAdenosine and Its Receptors in the Pathogenesis and Treatment of Inflammatory Skin Diseases
Chen, L., Xuan, L., & Mahnke, K. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115810 · Cited by 24 · see citing works
Reduced Proteasome Activity and Enhanced Autophagy in Blood Cells of Psoriatic Patients
Karabowicz, P., Wroński, A., Ostrowska, H., Waeg, G., Žarković, N., & Skrzydlewska, E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207608 · Cited by 20 · see citing works
Cavallini, M., Luca, C. D., Prussia, G., & Raichi, M. (2021) · Journal of Cosmetic Dermatology · doi:10.1111/jocd.14578 · Cited by 19 · see citing works
RetractedKim, S. T. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17081024 · Cited by 18 · see citing works
Koycheva, I. K., Marchev, A. S., Stoykova, I. D., & Georgiev, M. I. (2023) · Phytochemistry Reviews · doi:10.1007/s11101-023-09886-9 · Cited by 15 · see citing works
Dobrzyńska, I., Szachowicz‐Petelska, B., Wroński, A., Jarocka-Karpowicz, I., & Skrzydlewska, E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239129 · Cited by 15 · see citing works
Ceravolo, I., Mannino, F., Irrera, N., Minutoli, L., Arcoraci, V., Altavilla, D., Cavallini, G. M., Guarini, S., Squadrito, F., & Pallio, G. (2022) · Pharmaceuticals · doi:10.3390/ph15040447 · Cited by 15 · see citing works
Self-citationMannino, F., Pallio, G., Bitto, A., Altavilla, D., Minutoli, L., Squadrito, V., Arcoraci, V., Giorgi, D. A., Pirrotta, I., Squadrito, F., et al. (2021) · Pharmaceuticals · doi:10.3390/ph14080728 · Cited by 14 · see citing works
Self-citationZhang, Y., Song, J., Jiang, J., Yin, S., Luo, Y., Luo, Y., Ding, X., Ru, Y., Liu, L., Li, W., et al. (2021) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2021.114485 · Cited by 14 · see citing works
Park, S., Baek, S., Shin, H.-J., Kim, J.-S., Gwon, H.-I., 배승희, & An, S. (2025) · Applied Sciences · doi:10.3390/app151910437 · Cited by 12 · see citing works
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Vinardell, M. P. (2021) · Experimental Dermatology · doi:10.1111/exd.14479 · Cited by 12 · see citing works
Hasan, A. M., & Gatea, F. K. (2024) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-024-02947-6 · Cited by 12 · see citing works
Yun, J. Y., Park, S., Park, H. Y., & Lee, K. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24031932 · Cited by 11 · see citing works
Research Progress of m6A RNA Methylation in Skin Diseases
Liu, C., Wang, X., Yang, S., & Cao, S. (2023) · BioMed Research International · doi:10.1155/2023/3091204 · Cited by 9 · see citing works
Jang, S. K., Choi, J., Lim, H. W., Kim, H.-G., & Yoo, Y. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26125703 · Cited by 8 · see citing works
Ku, J. H., Yun, P., & Jeong, Y. K. (2026) · Tissue Engineering and Regenerative Medicine · doi:10.1007/s13770-025-00776-z · Cited by 8 · see citing works
Yang, Y., Liu, S., & Xiao, X. (2024) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-024-01620-2 · Cited by 7 · see citing works
Polynucleotide Mixture Attenuates Ultraviolet B-Induced Skin Pigmentation
Oh, S., Jeon, H.-D., Rho, N., Son, K. H., & Byun, K. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26136399 · Cited by 6 · see citing works
Jung, C. J., Lee, W. J., Won, C. H., Lee, M. W., & Chang, S. E. (2023) · Annals of Dermatology · doi:10.5021/ad.21a.038 · Cited by 5 · see citing works
Akaberi, S. M., Sharma, K., Ahmadi-Ashtiani, H. R., & Hedayati, M. (2025) · Journal of Skin and Stem Cell · doi:10.5812/jssc-159728 · Cited by 5 · see citing works
Special Issue: G Protein-Coupled Adenosine Receptors: Molecular Aspects and Beyond
Ciruela, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21061997 · Cited by 5 · see citing works
Nucleic Acid-Based Therapeutics for Periodontal Tissue Regeneration: A Comprehensive Review
Kim, J.-Y., Hong, M., Kim, S., & Garagiola, U. M. (2025) · Applied Sciences · doi:10.3390/app152111655 · Cited by 4 · see citing works
Xiao, W., Xu, P., Liu, A., Xu, K., & Sun, L. (2025) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2025.107177 · Cited by 4 · see citing works
Polynucleotides and polydeoxyribonucleotides in dermatology – A narrative review
Arora, G. (2025) · Journal of Cutaneous and Aesthetic Surgery · doi:10.25259/jcas_65_2025 · Cited by 3 · see citing works
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Shevchenko, N. A., Komarova, E. F., & Voloshin, R. N. (2025) · Современные проблемы науки и образования · doi:10.17513/spno.34048 · Cited by 2 · see citing works
de Araújo, L. P., Silva, E. N., Corsetti, P. P., Tagliati, C. A., da Silveira, N. J. F., & de Almeida, L. A. (2025) · BMC Methods · doi:10.1186/s44330-025-00036-5 · Cited by 2 · see citing works
Etemadi, N., Varshosaz, J., Shamaeizadeh, N., Mohamadsharifi, A., & Minaiyan, M. (2025) · International Journal of Pharmaceutics X · doi:10.1016/j.ijpx.2025.100462 · Cited by 2 · see citing works
Mou, P., Li, J., Li, C., Liu, X., Luo, X., Huang, R., Zhang, Y., & Wu, B. (2024) · Brazilian Journal of Poultry Science · doi:10.1590/1806-9061-2023-1899 · Cited by 1 · see citing works
Cai, Y., Dai, W., Liu, F., Li, Z., & Liu, G. (2026) · Clinical Cosmetic and Investigational Dermatology · doi:10.2147/ccid.s589176 · Cited by 1 · see citing works
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- Authors
- Irrera, N., Bitto, A., Vaccaro, M., Mannino, F., Squadrito, V., Pallio, G., Arcoraci, V., Minutoli, L., Ieni, A., Lentini, M., Altavilla, D., & Squadrito, F.
- Affiliations
- University of Messina (IT)
- Corresponding author
- Squadrito, Francesco
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2020-02-12
- Volume
- 21
- Issue
- 4
- Pages
- 1215
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC7072802
- OpenAlex
- W3006626493
- Cited by
- 41
- References
- 25
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 4 · 2023: 6 · 2022: 2 · 2021: 7 · 2020: 4
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Keywords
- polydeoxyribonucleotide, psoriasis, imiquimod-induced psoriasis, NF-κB signaling, Wnt/β-catenin signaling, adenosine A2A receptor, istradefylline, inflammatory cytokines, IL-10, interleukin-2, keratinocytes, skin inflammation, anti-inflammatory therapy
- MeSH terms
- Imiquimod, Animals, Disease Models, Animal, Mice, Inbred BALB C, Polydeoxyribonucleotides, Psoriasis, Skin, Keratinocytes, Cytokines, NF-kappa B, Receptor, Adenosine A2A, beta Catenin, Mice, Wnt Signaling Pathway
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