JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing

Abstract It has been shown that epigenetic regulation plays an important role in skin wound healing. We previously found that histone H3K27me3 demethylase JMJD3 regulates inflammation and cell migration in keratinocyte wound healing. In this study, we identified Notch1 as a direct target of JMJD3 an...

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Autores principales: Jungtae Na, Jee Yoon Shin, Hayan Jeong, Jee Youn Lee, Beom Joon Kim, Won Sun Kim, Tae Young Yune, Bong-Gun Ju
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Publicado: Nature Portfolio 2017
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Acceso en línea:https://doaj.org/article/f2cde2a3be66455082ceaf75657918e5
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spelling oai:doaj.org-article:f2cde2a3be66455082ceaf75657918e52021-12-02T12:31:48ZJMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing10.1038/s41598-017-06750-72045-2322https://doaj.org/article/f2cde2a3be66455082ceaf75657918e52017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06750-7https://doaj.org/toc/2045-2322Abstract It has been shown that epigenetic regulation plays an important role in skin wound healing. We previously found that histone H3K27me3 demethylase JMJD3 regulates inflammation and cell migration in keratinocyte wound healing. In this study, we identified Notch1 as a direct target of JMJD3 and NF-κB in wounded keratinocytes using in vitro cell and in vivo animal models. We found that Notch1 is up-regulated in the wound edge and its expression is dependent on JMJD3 and NF-κB in wounded keratinocytes. We also found that Notch1 activates the expression of RhoU and PLAU gene, which are critical regulators of cell migration. Consistently, depletion or inactivation of Notch1 resulted in decreased filopodia formation, increased focal adhesion and actin stress fiber, leading to reduced keratinocyte migration and skin wound healing. Thus, our findings provide the molecular mechanism involving JMJD3/NF-κB-Notch pathway in keratinocyte wound healing.Jungtae NaJee Yoon ShinHayan JeongJee Youn LeeBeom Joon KimWon Sun KimTae Young YuneBong-Gun JuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Jungtae Na
Jee Yoon Shin
Hayan Jeong
Jee Youn Lee
Beom Joon Kim
Won Sun Kim
Tae Young Yune
Bong-Gun Ju
JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing
description Abstract It has been shown that epigenetic regulation plays an important role in skin wound healing. We previously found that histone H3K27me3 demethylase JMJD3 regulates inflammation and cell migration in keratinocyte wound healing. In this study, we identified Notch1 as a direct target of JMJD3 and NF-κB in wounded keratinocytes using in vitro cell and in vivo animal models. We found that Notch1 is up-regulated in the wound edge and its expression is dependent on JMJD3 and NF-κB in wounded keratinocytes. We also found that Notch1 activates the expression of RhoU and PLAU gene, which are critical regulators of cell migration. Consistently, depletion or inactivation of Notch1 resulted in decreased filopodia formation, increased focal adhesion and actin stress fiber, leading to reduced keratinocyte migration and skin wound healing. Thus, our findings provide the molecular mechanism involving JMJD3/NF-κB-Notch pathway in keratinocyte wound healing.
format article
author Jungtae Na
Jee Yoon Shin
Hayan Jeong
Jee Youn Lee
Beom Joon Kim
Won Sun Kim
Tae Young Yune
Bong-Gun Ju
author_facet Jungtae Na
Jee Yoon Shin
Hayan Jeong
Jee Youn Lee
Beom Joon Kim
Won Sun Kim
Tae Young Yune
Bong-Gun Ju
author_sort Jungtae Na
title JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing
title_short JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing
title_full JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing
title_fullStr JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing
title_full_unstemmed JMJD3 and NF-κB-dependent activation of Notch1 gene is required for keratinocyte migration during skin wound healing
title_sort jmjd3 and nf-κb-dependent activation of notch1 gene is required for keratinocyte migration during skin wound healing
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/f2cde2a3be66455082ceaf75657918e5
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