1. Topical 5-azacytidine accelerates skin wound healing in rats.
- Author
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Gomes FS, de-Souza GF, Nascimento LF, Arantes EL, Pedro RM, Vitorino DC, Nunez CE, Melo Lima MH, Velloso LA, and Araújo EP
- Subjects
- Activins drug effects, Administration, Cutaneous, Animals, Gene Expression drug effects, Interleukin-10 metabolism, Keratinocytes drug effects, Keratinocytes metabolism, Keratins drug effects, Keratins metabolism, Male, Protein Precursors drug effects, Protein Precursors metabolism, Rats, Rats, Wistar, Signal Transduction drug effects, Transforming Growth Factor beta drug effects, Transforming Growth Factor beta metabolism, Tumor Necrosis Factor-alpha drug effects, Tumor Necrosis Factor-alpha metabolism, Azacitidine pharmacology, Cell Proliferation drug effects, Enzyme Inhibitors pharmacology, Follistatin drug effects, Skin injuries, Wound Healing drug effects
- Abstract
The development of new methods to improve skin wound healing may affect the outcomes of a number of medical conditions. Here, we evaluate the molecular and clinical effects of topical 5-azacytidine on wound healing in rats. 5-Azacytidine decreases the expression of follistatin-1, which negatively regulates activins. Activins, in turn, promote cell growth in different tissues, including the skin. Eight-week-old male Wistar rats were submitted to 8.0-mm punch-wounding in the dorsal region. After 3 days, rats were randomly assigned to receive either a control treatment or the topical application of a solution containing 5-azacytidine (10 mM) once per day. Photo documentation and sample collection were performed on days 5, 9, and 15. Overall, 5-azacytidine promoted a significant acceleration of complete wound healing (99.7% ± 0.7.0 vs. 71.2% ± 2.8 on day 15; n = 10; p < 0.01), accompanied by up to threefold reduction in follistatin expression. Histological examination of the skin revealed efficient reepithelization and cell proliferation, as evaluated by the BrdU incorporation method. 5-Azacytidine treatment also resulted in increased gene expression of transforming growth factor-beta and the keratinocyte markers involucrin and cytokeratin, as well as decreased expression of cytokines such as tumor necrosis factor-alpha and interleukin-10. Lastly, when recombinant follistatin was applied to the skin in parallel with topical 5-azacytidine, most of the beneficial effects of the drug were lost. Thus, 5-azacytidine acts, at least in part through the follistatin/activin pathway, to improve skin wound healing in rodents., (© 2014 by the Wound Healing Society.)
- Published
- 2014
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