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Valproic Acid Induces Cutaneous Wound Healing In Vivo and Enhances Keratinocyte Motility

BACKGROUND: Cutaneous wound healing is a complex process involving several signaling pathways such as the Wnt and extracellular signal-regulated kinase (ERK) signaling pathways. Valproic acid (VPA) is a commonly used antiepileptic drug that acts on these signaling pathways; however, the effect of VP...

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Autores principales: Lee, Soung-Hoon, Zahoor, Muhammad, Hwang, Jae-Kwan, Min, Do Sik, Choi, Kang-Yell
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492241/
https://www.ncbi.nlm.nih.gov/pubmed/23144972
http://dx.doi.org/10.1371/journal.pone.0048791
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author Lee, Soung-Hoon
Zahoor, Muhammad
Hwang, Jae-Kwan
Min, Do Sik
Choi, Kang-Yell
author_facet Lee, Soung-Hoon
Zahoor, Muhammad
Hwang, Jae-Kwan
Min, Do Sik
Choi, Kang-Yell
author_sort Lee, Soung-Hoon
collection PubMed
description BACKGROUND: Cutaneous wound healing is a complex process involving several signaling pathways such as the Wnt and extracellular signal-regulated kinase (ERK) signaling pathways. Valproic acid (VPA) is a commonly used antiepileptic drug that acts on these signaling pathways; however, the effect of VPA on cutaneous wound healing is unknown. METHODS AND FINDINGS: We created full-thickness wounds on the backs of C3H mice and then applied VPA. After 7 d, we observed marked healing and reduced wound size in VPA-treated mice. In the neo-epidermis of the wounds, β-catenin and markers for keratinocyte terminal differentiation were increased after VPA treatment. In addition, α-smooth muscle actin (α-SMA), collagen I and collagen III in the wounds were significantly increased. VPA induced proliferation and suppressed apoptosis of cells in the wounds, as determined by Ki67 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining analyses, respectively. In vitro, VPA enhanced the motility of HaCaT keratinocytes by activating Wnt/β-catenin, ERK and phosphatidylinositol 3-kinase (PI3-kinase)/Akt signaling pathways. CONCLUSIONS: VPA enhances cutaneous wound healing in a murine model and induces migration of HaCaT keratinocytes.
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spelling pubmed-34922412012-11-09 Valproic Acid Induces Cutaneous Wound Healing In Vivo and Enhances Keratinocyte Motility Lee, Soung-Hoon Zahoor, Muhammad Hwang, Jae-Kwan Min, Do Sik Choi, Kang-Yell PLoS One Research Article BACKGROUND: Cutaneous wound healing is a complex process involving several signaling pathways such as the Wnt and extracellular signal-regulated kinase (ERK) signaling pathways. Valproic acid (VPA) is a commonly used antiepileptic drug that acts on these signaling pathways; however, the effect of VPA on cutaneous wound healing is unknown. METHODS AND FINDINGS: We created full-thickness wounds on the backs of C3H mice and then applied VPA. After 7 d, we observed marked healing and reduced wound size in VPA-treated mice. In the neo-epidermis of the wounds, β-catenin and markers for keratinocyte terminal differentiation were increased after VPA treatment. In addition, α-smooth muscle actin (α-SMA), collagen I and collagen III in the wounds were significantly increased. VPA induced proliferation and suppressed apoptosis of cells in the wounds, as determined by Ki67 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining analyses, respectively. In vitro, VPA enhanced the motility of HaCaT keratinocytes by activating Wnt/β-catenin, ERK and phosphatidylinositol 3-kinase (PI3-kinase)/Akt signaling pathways. CONCLUSIONS: VPA enhances cutaneous wound healing in a murine model and induces migration of HaCaT keratinocytes. Public Library of Science 2012-11-07 /pmc/articles/PMC3492241/ /pubmed/23144972 http://dx.doi.org/10.1371/journal.pone.0048791 Text en © 2012 Lee et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lee, Soung-Hoon
Zahoor, Muhammad
Hwang, Jae-Kwan
Min, Do Sik
Choi, Kang-Yell
Valproic Acid Induces Cutaneous Wound Healing In Vivo and Enhances Keratinocyte Motility
title Valproic Acid Induces Cutaneous Wound Healing In Vivo and Enhances Keratinocyte Motility
title_full Valproic Acid Induces Cutaneous Wound Healing In Vivo and Enhances Keratinocyte Motility
title_fullStr Valproic Acid Induces Cutaneous Wound Healing In Vivo and Enhances Keratinocyte Motility
title_full_unstemmed Valproic Acid Induces Cutaneous Wound Healing In Vivo and Enhances Keratinocyte Motility
title_short Valproic Acid Induces Cutaneous Wound Healing In Vivo and Enhances Keratinocyte Motility
title_sort valproic acid induces cutaneous wound healing in vivo and enhances keratinocyte motility
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3492241/
https://www.ncbi.nlm.nih.gov/pubmed/23144972
http://dx.doi.org/10.1371/journal.pone.0048791
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