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Insulin and TOR signal in parallel through FOXO and S6K to promote epithelial wound healing

Kakanj, P; Moussian, B; Groenke, S; Bustos, V; Eming, SA; Partridge, L; Leptin, M; (2016) Insulin and TOR signal in parallel through FOXO and S6K to promote epithelial wound healing. Nature Communications , 7 , Article 12972. 10.1038/ncomms12972. Green open access

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Abstract

The TOR and Insulin/IGF signalling (IIS) network controls growth, metabolism and ageing. Although reducing TOR or insulin signalling can be beneficial for ageing, it can be detrimental for wound healing, but the reasons for this difference are unknown. Here we show that IIS is activated in the cells surrounding an epidermal wound in Drosophila melanogaster larvae, resulting in PI3K activation and redistribution of the transcription factor FOXO. Insulin and TOR signalling are independently necessary for normal wound healing, with FOXO and S6K as their respective effectors. IIS is specifically required in cells surrounding the wound, and the effect is independent of glycogen metabolism. Insulin signalling is needed for the efficient assembly of an actomyosin cable around the wound, and constitutively active myosin II regulatory light chain suppresses the effects of reduced IIS. These findings may have implications for the role of insulin signalling and FOXO activation in diabetic wound healing.

Type: Article
Title: Insulin and TOR signal in parallel through FOXO and S6K to promote epithelial wound healing
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/ncomms12972
Publisher version: http://doi.org/10.1038/ncomms12972
Language: English
Additional information: © The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, DROSOPHILA-MELANOGASTER, FAT-BODY, CELL-DEATH, LIFE-SPAN, EXPRESSION, CLOSURE, LARVAE, DFOXO, SKIN, MTOR
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: http://discovery.ucl.ac.uk/id/eprint/1524779
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