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Title: | microRNA-155 inhibition restores Fibroblast Growth Factor 7 expression in diabetic skin and decreases wound inflammation | Authors: | 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 |
Issue Date: | 9-Apr-2019 | Publisher: | Springer Nature | Project: | SFRH/BPD/112883/2015 CENTRO-01-0145-FEDER-000012/HealthyAging2020 |
metadata.degois.publication.title: | Scientific Reports | metadata.degois.publication.volume: | 9 | metadata.degois.publication.issue: | 1 | Abstract: | 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 | Rights: | openAccess |
Appears in Collections: | FMUC Medicina - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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