microRNA-155 inhibition restores Fibroblast Growth Factor 7 expression in diabetic skin and decreases wound inflammation
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/107371 https://doi.org/10.1038/s41598-019-42309-4 |
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. |
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microRNA-155 inhibition restores Fibroblast Growth Factor 7 expression in diabetic skin and decreases wound inflammationAnimalsDiabetes Mellitus, ExperimentalDiabetic FootFibroblast Growth Factor 7HumansKeratinocytesMaleMiceMicroRNAsRe-EpithelializationWound HealingUp-RegulationTreatment 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.Springer Nature2019-04-09info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107371http://hdl.handle.net/10316/107371https://doi.org/10.1038/s41598-019-42309-4eng2045-2322Moura, JoãoSørensen, AnjaLeal, ErmelindoSvendsen, RikkeCarvalho, LinaWillemoes, Rie JuulJørgensen, Per TrolleJenssen, HåvardWengel, JesperDalgaard, Louise TorpCarvalho, Eugeniainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-06T10:22:38Zoai:estudogeral.uc.pt:10316/107371Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:23:44.131083Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
microRNA-155 inhibition restores Fibroblast Growth Factor 7 expression in diabetic skin and decreases wound inflammation |
title |
microRNA-155 inhibition restores Fibroblast Growth Factor 7 expression in diabetic skin and decreases wound inflammation |
spellingShingle |
microRNA-155 inhibition restores Fibroblast Growth Factor 7 expression in diabetic skin and decreases wound inflammation Moura, João Animals Diabetes Mellitus, Experimental Diabetic Foot Fibroblast Growth Factor 7 Humans Keratinocytes Male Mice MicroRNAs Re-Epithelialization Wound Healing Up-Regulation |
title_short |
microRNA-155 inhibition restores Fibroblast Growth Factor 7 expression in diabetic skin and decreases wound inflammation |
title_full |
microRNA-155 inhibition restores Fibroblast Growth Factor 7 expression in diabetic skin and decreases wound inflammation |
title_fullStr |
microRNA-155 inhibition restores Fibroblast Growth Factor 7 expression in diabetic skin and decreases wound inflammation |
title_full_unstemmed |
microRNA-155 inhibition restores Fibroblast Growth Factor 7 expression in diabetic skin and decreases wound inflammation |
title_sort |
microRNA-155 inhibition restores Fibroblast Growth Factor 7 expression in diabetic skin and decreases wound inflammation |
author |
Moura, João |
author_facet |
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 |
author_role |
author |
author2 |
Sørensen, Anja Leal, Ermelindo Svendsen, Rikke Carvalho, Lina Willemoes, Rie Juul Jørgensen, Per Trolle Jenssen, Håvard Wengel, Jesper Dalgaard, Louise Torp Carvalho, Eugenia |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
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 |
dc.subject.por.fl_str_mv |
Animals Diabetes Mellitus, Experimental Diabetic Foot Fibroblast Growth Factor 7 Humans Keratinocytes Male Mice MicroRNAs Re-Epithelialization Wound Healing Up-Regulation |
topic |
Animals Diabetes Mellitus, Experimental Diabetic Foot Fibroblast Growth Factor 7 Humans Keratinocytes Male Mice MicroRNAs Re-Epithelialization Wound Healing Up-Regulation |
description |
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. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-04-09 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/107371 http://hdl.handle.net/10316/107371 https://doi.org/10.1038/s41598-019-42309-4 |
url |
http://hdl.handle.net/10316/107371 https://doi.org/10.1038/s41598-019-42309-4 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2045-2322 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134123794628608 |