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

Soung Hoon Lee, Muhammad Zahoor, Jae-Kwan Hwang, Do Sik Min, Kang-Yell Choi

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere48791
JournalPLoS One
Volume7
Issue number11
DOIs
Publication statusPublished - 2012 Nov 7

Fingerprint

valproic acid
keratinocytes
Valproic Acid
tissue repair
Keratinocytes
Wound Healing
Skin
Catenins
Extracellular Signal-Regulated MAP Kinases
Wounds and Injuries
mitogen-activated protein kinase
collagen
Collagen
Phosphatidylinositol 3-Kinase
anticonvulsants
DNA Nucleotidylexotransferase
Inbred C3H Mouse
mice
back (body region)
phosphatidylinositol 3-kinase

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

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title = "Valproic Acid Induces Cutaneous Wound Healing In Vivo and Enhances Keratinocyte Motility",
abstract = "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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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.

In: PLoS One, Vol. 7, No. 11, e48791, 07.11.2012.

Research output: Contribution to journalArticle

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T1 - Valproic Acid Induces Cutaneous Wound Healing In Vivo and Enhances Keratinocyte Motility

AU - Lee, Soung Hoon

AU - Zahoor, Muhammad

AU - Hwang, Jae-Kwan

AU - Min, Do Sik

AU - Choi, Kang-Yell

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N2 - 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.

AB - 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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