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Examination of epigenetic inhibitor zebularine in treatment of skin wounds in healthy and diabetic mice
Abstract
DNA methyltransferase inhibitor zebularine was proven to induce regeneration in the ear pinna in mice. We utilized a dorsal skin wound model to further evaluate this epigenetic inhibitor in wound healing. Full-thickness excisional wounds were made on the dorsum of 2 and 10-month-old healthy BALB/c and 3 and 8-month-old diabetic (db/db) mice, followed by topical or intraperitoneal zebularine delivery. Depending on the strain, age, dose, and delivery, the zebularine treatments either had no effect or accelerated or delayed wound closure. In principle, zebularine applied topically moderately promoted wound closure in the healthy but markedly delayed in the diabetic mice, which was in line with decreased viability of cultured keratinocytes from diabetic patients exposed to zebularine. The histological analysis revealed an improvement in the architecture of restored skin in zebularine-treated mice, manifested as a distinct layered pattern resembling panniculus carnosus. The finding corresponds with the zebularine-mediated activation of the Wnt5a gene, an essential regulator of Wnt signaling, the pathway involved in hair follicle development, the process which in turn is connected with regenerative skin healing. Although zebularine did not remarkably accelerate wound healing, zebularine and other epigenetic inhibitors deserve further testing as potential drugs to improve the quality of restored skin.
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Authors (9)
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Milena Deptuła
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Aneta Skoniecka
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Jacek Zieliński dr hab.
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Sylwia Rodziewicz‐Motowidło
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Michał Pikuła dr hab. med.
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- Publication version
- Accepted or Published Version
- DOI:
- Digital Object Identifier (open in new tab) 10.1002/term.3365
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- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
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Journal of Tissue Engineering and Regenerative Medicine
no. 16,
pages 1238 - 1248,
ISSN: 1932-6254 - Language:
- English
- Publication year:
- 2022
- Bibliographic description:
- Sass P., Sosnowski P., Kamińska J., Deptuła M., Skoniecka A., Zieliński J., Rodziewicz‐motowidło S., Pikuła M., Sachadyn P.: Examination of epigenetic inhibitor zebularine in treatment of skin wounds in healthy and diabetic mice// Journal of Tissue Engineering and Regenerative Medicine -Vol. 16,iss. 12 (2022), s.1238-1248
- DOI:
- Digital Object Identifier (open in new tab) 10.1002/term.3365
- Sources of funding:
- Verified by:
- Gdańsk University of Technology
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