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Foxo1 Inhibits Diabetic Mucosal Wound Healing but Enhances Healing of Normoglycemic Wounds
Re-epithelialization is an important part in mucosal wound healing. Surprisingly little is known about the impact of diabetes on the molecular events of mucosal healing. We examined the role of the transcription factor forkhead box O1 (Foxo1) in oral wounds of diabetic and normoglycemic mice with ke...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274809/ https://www.ncbi.nlm.nih.gov/pubmed/25187373 http://dx.doi.org/10.2337/db14-0589 |
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author | Xu, Fanxing Othman, Badr Lim, Jason Batres, Angelika Ponugoti, Bhaskar Zhang, Chenying Yi, Leah Liu, Jian Tian, Chen Hameedaldeen, Alhassan Alsadun, Sarah Tarapore, Rohinton Graves, Dana T. |
author_facet | Xu, Fanxing Othman, Badr Lim, Jason Batres, Angelika Ponugoti, Bhaskar Zhang, Chenying Yi, Leah Liu, Jian Tian, Chen Hameedaldeen, Alhassan Alsadun, Sarah Tarapore, Rohinton Graves, Dana T. |
author_sort | Xu, Fanxing |
collection | PubMed |
description | Re-epithelialization is an important part in mucosal wound healing. Surprisingly little is known about the impact of diabetes on the molecular events of mucosal healing. We examined the role of the transcription factor forkhead box O1 (Foxo1) in oral wounds of diabetic and normoglycemic mice with keratinocyte-specific Foxo1 deletion. Diabetic mucosal wounds had significantly delayed healing with reduced cell migration and proliferation. Foxo1 deletion rescued the negative impact of diabetes on healing but had the opposite effect in normoglycemic mice. Diabetes in vivo and in high glucose conditions in vitro enhanced expression of chemokine (C-C motif) ligand 20 (CCL20) and interleukin-36γ (IL-36γ) in a Foxo1-dependent manner. High glucose–stimulated Foxo1 binding to CCL20 and IL-36γ promoters and CCL20 and IL-36γ significantly inhibited migration of these cells in high glucose conditions. In normal healing, Foxo1 was needed for transforming growth factor-β1 (TGF-β1) expression, and in standard glucose conditions, TGF-β1 rescued the negative effect of Foxo1 silencing on migration in vitro. We propose that Foxo1 under diabetic or high glucose conditions impairs healing by promoting high levels of CCL20 and IL-36γ expression but under normal conditions, enhances it by inducing TGF-β1. This finding provides mechanistic insight into how Foxo1 mediates the impact of diabetes on mucosal wound healing. |
format | Online Article Text |
id | pubmed-4274809 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-42748092016-01-01 Foxo1 Inhibits Diabetic Mucosal Wound Healing but Enhances Healing of Normoglycemic Wounds Xu, Fanxing Othman, Badr Lim, Jason Batres, Angelika Ponugoti, Bhaskar Zhang, Chenying Yi, Leah Liu, Jian Tian, Chen Hameedaldeen, Alhassan Alsadun, Sarah Tarapore, Rohinton Graves, Dana T. Diabetes Complications Re-epithelialization is an important part in mucosal wound healing. Surprisingly little is known about the impact of diabetes on the molecular events of mucosal healing. We examined the role of the transcription factor forkhead box O1 (Foxo1) in oral wounds of diabetic and normoglycemic mice with keratinocyte-specific Foxo1 deletion. Diabetic mucosal wounds had significantly delayed healing with reduced cell migration and proliferation. Foxo1 deletion rescued the negative impact of diabetes on healing but had the opposite effect in normoglycemic mice. Diabetes in vivo and in high glucose conditions in vitro enhanced expression of chemokine (C-C motif) ligand 20 (CCL20) and interleukin-36γ (IL-36γ) in a Foxo1-dependent manner. High glucose–stimulated Foxo1 binding to CCL20 and IL-36γ promoters and CCL20 and IL-36γ significantly inhibited migration of these cells in high glucose conditions. In normal healing, Foxo1 was needed for transforming growth factor-β1 (TGF-β1) expression, and in standard glucose conditions, TGF-β1 rescued the negative effect of Foxo1 silencing on migration in vitro. We propose that Foxo1 under diabetic or high glucose conditions impairs healing by promoting high levels of CCL20 and IL-36γ expression but under normal conditions, enhances it by inducing TGF-β1. This finding provides mechanistic insight into how Foxo1 mediates the impact of diabetes on mucosal wound healing. American Diabetes Association 2015-01 2014-09-03 /pmc/articles/PMC4274809/ /pubmed/25187373 http://dx.doi.org/10.2337/db14-0589 Text en © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. |
spellingShingle | Complications Xu, Fanxing Othman, Badr Lim, Jason Batres, Angelika Ponugoti, Bhaskar Zhang, Chenying Yi, Leah Liu, Jian Tian, Chen Hameedaldeen, Alhassan Alsadun, Sarah Tarapore, Rohinton Graves, Dana T. Foxo1 Inhibits Diabetic Mucosal Wound Healing but Enhances Healing of Normoglycemic Wounds |
title | Foxo1 Inhibits Diabetic Mucosal Wound Healing but Enhances Healing of Normoglycemic Wounds |
title_full | Foxo1 Inhibits Diabetic Mucosal Wound Healing but Enhances Healing of Normoglycemic Wounds |
title_fullStr | Foxo1 Inhibits Diabetic Mucosal Wound Healing but Enhances Healing of Normoglycemic Wounds |
title_full_unstemmed | Foxo1 Inhibits Diabetic Mucosal Wound Healing but Enhances Healing of Normoglycemic Wounds |
title_short | Foxo1 Inhibits Diabetic Mucosal Wound Healing but Enhances Healing of Normoglycemic Wounds |
title_sort | foxo1 inhibits diabetic mucosal wound healing but enhances healing of normoglycemic wounds |
topic | Complications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4274809/ https://www.ncbi.nlm.nih.gov/pubmed/25187373 http://dx.doi.org/10.2337/db14-0589 |
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