Skin wound closure delay in metabolic syndrome correlates with SCF deficiency in keratinocytes

Abstract 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 wou...

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Autores principales:	Zhenping Wang, Yanhan Wang, Nicholas Bradbury, Carolina Gonzales Bravo, Bernd Schnabl, Anna Di Nardo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/098cf2d311444ce9964d205322752c1f
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spelling	oai:doaj.org-article:098cf2d311444ce9964d205322752c1f2021-12-02T15:11:53ZSkin wound closure delay in metabolic syndrome correlates with SCF deficiency in keratinocytes10.1038/s41598-020-78244-y2045-2322https://doaj.org/article/098cf2d311444ce9964d205322752c1f2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78244-yhttps://doaj.org/toc/2045-2322Abstract 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.Zhenping WangYanhan WangNicholas BradburyCarolina Gonzales BravoBernd SchnablAnna Di NardoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zhenping Wang Yanhan Wang Nicholas Bradbury Carolina Gonzales Bravo Bernd Schnabl Anna Di Nardo Skin wound closure delay in metabolic syndrome correlates with SCF deficiency in keratinocytes
description	Abstract 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	article
author	Zhenping Wang Yanhan Wang Nicholas Bradbury Carolina Gonzales Bravo Bernd Schnabl Anna Di Nardo
author_facet	Zhenping Wang Yanhan Wang Nicholas Bradbury Carolina Gonzales Bravo Bernd Schnabl Anna Di Nardo
author_sort	Zhenping Wang
title	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_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_sort	skin wound closure delay in metabolic syndrome correlates with scf deficiency in keratinocytes
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/098cf2d311444ce9964d205322752c1f
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Skin wound closure delay in metabolic syndrome correlates with SCF deficiency in keratinocytes

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