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The Influence of Flightless I on Toll-Like-Receptor-Mediated Inflammation in a Murine Model of Diabetic Wound Healing
Impaired wound healing and ulceration represent a serious complication of both type 1 and type 2 diabetes. Cytoskeletal protein Flightless I (Flii) is an important inhibitor of wound repair, and reduced Flii gene expression in fibroblasts increased migration, proliferation, and adhesion. As such it...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595111/ https://www.ncbi.nlm.nih.gov/pubmed/23555084 http://dx.doi.org/10.1155/2013/389792 |
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author | Ruzehaji, Nadira Mills, Stuart J. Melville, Elizabeth Arkell, Ruth Fitridge, Robert Cowin, Allison J. |
author_facet | Ruzehaji, Nadira Mills, Stuart J. Melville, Elizabeth Arkell, Ruth Fitridge, Robert Cowin, Allison J. |
author_sort | Ruzehaji, Nadira |
collection | PubMed |
description | Impaired wound healing and ulceration represent a serious complication of both type 1 and type 2 diabetes. Cytoskeletal protein Flightless I (Flii) is an important inhibitor of wound repair, and reduced Flii gene expression in fibroblasts increased migration, proliferation, and adhesion. As such it has the ability to influence all phases of wound healing including inflammation, remodelling and angiogenesis. Flii has the potential to modulate inflammation through its interaction with MyD88 which it an adaptor protein for TLR4. To assess the effect of Flii on the inflammatory response of diabetic wounds, we used a murine model of streptozocin-induced diabetes and Flii genetic mice. Increased levels of Flii were detected in Flii transgenic murine wounds resulting in impaired healing which was exacerbated when diabetes was induced. When Flii levels were reduced in diabetic wounds of Flii-deficient mice, healing was improved and decreased levels of TLR4 were observed. In contrast, increasing the level of Flii in diabetic mouse wounds led to increased TLR4 and NF-κB production. Treatment of murine diabetic wounds with neutralising antibodies to Flii led to an improvement in healing with decreased expression of TLR4. Decreasing the level of Flii in diabetic wounds may therefore reduce the inflammatory response and improve healing. |
format | Online Article Text |
id | pubmed-3595111 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-35951112013-04-02 The Influence of Flightless I on Toll-Like-Receptor-Mediated Inflammation in a Murine Model of Diabetic Wound Healing Ruzehaji, Nadira Mills, Stuart J. Melville, Elizabeth Arkell, Ruth Fitridge, Robert Cowin, Allison J. Biomed Res Int Research Article Impaired wound healing and ulceration represent a serious complication of both type 1 and type 2 diabetes. Cytoskeletal protein Flightless I (Flii) is an important inhibitor of wound repair, and reduced Flii gene expression in fibroblasts increased migration, proliferation, and adhesion. As such it has the ability to influence all phases of wound healing including inflammation, remodelling and angiogenesis. Flii has the potential to modulate inflammation through its interaction with MyD88 which it an adaptor protein for TLR4. To assess the effect of Flii on the inflammatory response of diabetic wounds, we used a murine model of streptozocin-induced diabetes and Flii genetic mice. Increased levels of Flii were detected in Flii transgenic murine wounds resulting in impaired healing which was exacerbated when diabetes was induced. When Flii levels were reduced in diabetic wounds of Flii-deficient mice, healing was improved and decreased levels of TLR4 were observed. In contrast, increasing the level of Flii in diabetic mouse wounds led to increased TLR4 and NF-κB production. Treatment of murine diabetic wounds with neutralising antibodies to Flii led to an improvement in healing with decreased expression of TLR4. Decreasing the level of Flii in diabetic wounds may therefore reduce the inflammatory response and improve healing. Hindawi Publishing Corporation 2013 2013-02-18 /pmc/articles/PMC3595111/ /pubmed/23555084 http://dx.doi.org/10.1155/2013/389792 Text en Copyright © 2013 Nadira Ruzehaji et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Ruzehaji, Nadira Mills, Stuart J. Melville, Elizabeth Arkell, Ruth Fitridge, Robert Cowin, Allison J. The Influence of Flightless I on Toll-Like-Receptor-Mediated Inflammation in a Murine Model of Diabetic Wound Healing |
title | The Influence of Flightless I on Toll-Like-Receptor-Mediated Inflammation in a Murine Model of Diabetic Wound Healing |
title_full | The Influence of Flightless I on Toll-Like-Receptor-Mediated Inflammation in a Murine Model of Diabetic Wound Healing |
title_fullStr | The Influence of Flightless I on Toll-Like-Receptor-Mediated Inflammation in a Murine Model of Diabetic Wound Healing |
title_full_unstemmed | The Influence of Flightless I on Toll-Like-Receptor-Mediated Inflammation in a Murine Model of Diabetic Wound Healing |
title_short | The Influence of Flightless I on Toll-Like-Receptor-Mediated Inflammation in a Murine Model of Diabetic Wound Healing |
title_sort | influence of flightless i on toll-like-receptor-mediated inflammation in a murine model of diabetic wound healing |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595111/ https://www.ncbi.nlm.nih.gov/pubmed/23555084 http://dx.doi.org/10.1155/2013/389792 |
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