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.
  
  
  RESULTS
  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.
authors.affiliation: Translational Research Center for Protein Function Control, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul Korea.
authors.forename: Soung-Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Muhammad
authors.initials: M
authors.lastname: Zahoor
authors.forename: Jae-Kwan
authors.initials: JK
authors.lastname: Hwang
authors.forename: Do Sik
authors.initials: do S
authors.lastname: Min
authors.forename: Kang-Yell
authors.initials: KY
authors.lastname: Choi
mesh_terms: D000199:Actins; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D015603:Keratinocytes / Q000187:drug effects*; D020935:MAP Kinase Signaling System; D051379:Mice; D008809:Mice, Inbred C3H; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D051153:Wnt Proteins / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000199:Actins; D024042:Collagen Type I; D024061:Collagen Type III; D051153:Wnt Proteins; C544013:alpha-smooth muscle actin, mouse; D051176:beta Catenin; D014635:Valproic Acid; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt