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Skin wound closure delay in metabolic syndrome correlates with SCF deficiency in keratinocytes
Poor wound closure due to diabetes, aging, stress, obesity, alcoholism, and chronic disease affects millions of people worldwide. Reasons wounds will not close are still unclear, and current therapies are limited. Although stem cell factor (SCF), a cytokine, is known to be important for wound repair...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728784/ https://www.ncbi.nlm.nih.gov/pubmed/33303806 http://dx.doi.org/10.1038/s41598-020-78244-y |
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author | Wang, Zhenping Wang, Yanhan Bradbury, Nicholas Gonzales Bravo, Carolina Schnabl, Bernd Di Nardo, Anna |
author_facet | Wang, Zhenping Wang, Yanhan Bradbury, Nicholas Gonzales Bravo, Carolina Schnabl, Bernd Di Nardo, Anna |
author_sort | Wang, Zhenping |
collection | PubMed |
description | Poor wound closure due to diabetes, aging, stress, obesity, alcoholism, and chronic disease affects millions of people worldwide. Reasons wounds will not close are still unclear, and current therapies are limited. Although stem cell factor (SCF), a cytokine, is known to be important for wound repair, the cellular and molecular mechanisms of SCF in wound closure remain poorly understood. Here, we found that SCF expression in the epidermis is decreased in mouse models of delayed wound closure intended to mimic old age, obesity, and alcoholism. By using SCF conditionally knocked out mice, we demonstrated that keratinocytes’ autocrine production of SCF activates a transient c-kit receptor in keratinocytes. Transient activation of the c-kit receptor induces the expression of growth factors and chemokines to promote wound re-epithelialization by increasing migration of skin cells (keratinocytes and fibroblasts) and immune cells (neutrophils) to the wound bed 24–48 h post-wounding. Our results demonstrate that keratinocyte-produced SCF is essential to wound closure due to the increased recruitment of a unique combination of skin cells and immune cells in the early phase after wounding. This discovery is imperative for developing clinical strategies that might improve the body’s natural repair mechanisms for treating patients with wound-closure pathologies. |
format | Online Article Text |
id | pubmed-7728784 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-77287842020-12-14 Skin wound closure delay in metabolic syndrome correlates with SCF deficiency in keratinocytes Wang, Zhenping Wang, Yanhan Bradbury, Nicholas Gonzales Bravo, Carolina Schnabl, Bernd Di Nardo, Anna Sci Rep Article Poor wound closure due to diabetes, aging, stress, obesity, alcoholism, and chronic disease affects millions of people worldwide. Reasons wounds will not close are still unclear, and current therapies are limited. Although stem cell factor (SCF), a cytokine, is known to be important for wound repair, the cellular and molecular mechanisms of SCF in wound closure remain poorly understood. Here, we found that SCF expression in the epidermis is decreased in mouse models of delayed wound closure intended to mimic old age, obesity, and alcoholism. By using SCF conditionally knocked out mice, we demonstrated that keratinocytes’ autocrine production of SCF activates a transient c-kit receptor in keratinocytes. Transient activation of the c-kit receptor induces the expression of growth factors and chemokines to promote wound re-epithelialization by increasing migration of skin cells (keratinocytes and fibroblasts) and immune cells (neutrophils) to the wound bed 24–48 h post-wounding. Our results demonstrate that keratinocyte-produced SCF is essential to wound closure due to the increased recruitment of a unique combination of skin cells and immune cells in the early phase after wounding. This discovery is imperative for developing clinical strategies that might improve the body’s natural repair mechanisms for treating patients with wound-closure pathologies. Nature Publishing Group UK 2020-12-10 /pmc/articles/PMC7728784/ /pubmed/33303806 http://dx.doi.org/10.1038/s41598-020-78244-y Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Wang, Zhenping Wang, Yanhan Bradbury, Nicholas Gonzales Bravo, Carolina Schnabl, Bernd Di Nardo, Anna Skin wound closure delay in metabolic syndrome correlates with SCF deficiency in keratinocytes |
title | Skin wound closure delay in metabolic syndrome correlates with SCF deficiency in keratinocytes |
title_full | Skin wound closure delay in metabolic syndrome correlates with SCF deficiency in keratinocytes |
title_fullStr | Skin wound closure delay in metabolic syndrome correlates with SCF deficiency in keratinocytes |
title_full_unstemmed | Skin wound closure delay in metabolic syndrome correlates with SCF deficiency in keratinocytes |
title_short | Skin wound closure delay in metabolic syndrome correlates with SCF deficiency in keratinocytes |
title_sort | skin wound closure delay in metabolic syndrome correlates with scf deficiency in keratinocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728784/ https://www.ncbi.nlm.nih.gov/pubmed/33303806 http://dx.doi.org/10.1038/s41598-020-78244-y |
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