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Título: | microRNA-155 inhibition restores Fibroblast Growth Factor 7 expression in diabetic skin and decreases wound inflammation | Autor: | Moura, João Sørensen, Anja Leal, Ermelindo Svendsen, Rikke Carvalho, Lina Willemoes, Rie Juul Jørgensen, Per Trolle Jenssen, Håvard Wengel, Jesper Dalgaard, Louise Torp Carvalho, Eugenia |
Data: | 9-Abr-2019 | Editora: | Springer Nature | Projeto: | JM acknowledges a postdoctoral fellowship from the HealthyAging2020 project, CENTRO-01-0145-FEDER- 000012-N2323. ECL acknowledges a postdoctoral fellowship from the Portuguese Foundation for Science and Technology, SFRH/BPD/112883/2015. AES acknowledges a post doctoral fellowship from the Danish Diabetes Academy, supported by the Novo Nordisk Foundation. The authors would like to thank Christa Persson for dedicated and skilled technical expertise. This work was supported by the European Foundation for the Study of Diabetes to LTD, HJ and EC, the Danish Medical Research Council to LTD, GIFT/SPD to EC, HealthyAging2020 CENTRO-01-0145-FEDER-000012-N2323 to EC, as well as Pepper grant: P30 AG028718 and NIGMS_NIH P20GM109096 | Título da revista, periódico, livro ou evento: | Scientific Reports | Volume: | 9 | Número: | 1 | Resumo: | Treatment for chronic diabetic foot ulcers is limited by the inability to simultaneously address the excessive inflammation and impaired re-epithelization and remodeling. Impaired re-epithelization leads to significantly delayed wound closure and excessive inflammation causes tissue destruction, both enhancing wound pathogen colonization. Among many differentially expressed microRNAs, miR-155 is significantly upregulated and fibroblast growth factor 7 (FGF7) mRNA (target of miR-155) and protein are suppressed in diabetic skin, when compared to controls, leading us to hypothesize that topical miR-155 inhibition would improve diabetic wound healing by restoring FGF7 expression. In vitro inhibition of miR-155 increased human keratinocyte scratch closure and topical inhibition of miR-155 in vivo in wounds increased murine FGF7 protein expression and significantly enhanced diabetic wound healing. Moreover, we show that miR-155 inhibition leads to a reduction in wound inflammation, in accordance with known pro-inflammatory actions of miR-155. Our results demonstrate, for the first time, that topical miR-155 inhibition increases diabetic wound fibroblast growth factor 7 expression in diabetic wounds, which, in turn, increases re-epithelization and, consequently, accelerates wound closure. Topical miR-155 inhibition targets both excessive inflammation and impaired re-epithelization and remodeling, being a potentially new and effective treatment for chronic diabetic foot ulcers. | URI: | https://hdl.handle.net/10316/107371 | ISSN: | 2045-2322 | DOI: | 10.1038/s41598-019-42309-4 | Direitos: | openAccess |
Aparece nas coleções: | FMUC Medicina - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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microRNA155-inhibition-restores-Fibroblast-Growth-Factor-7-expression-in-diabetic-skin-and-decreases-wound-inflammationScientific-Reports.pdf | 3.32 MB | Adobe PDF | Ver/Abrir |
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