Comparative transcriptomic profiling of hydrogen peroxide signaling networks in zebrafish and human keratinocytes: Implications toward conservation, migration and wound healing

Sci Rep. 2016 Feb 5;6:20328. doi: 10.1038/srep20328.


Skin wounds need to be repaired rapidly after injury to restore proper skin barrier function. Hydrogen peroxide (H2O2) is a conserved signaling factor that has been shown to promote a variety of skin wound repair processes, including immune cell migration, angiogenesis and sensory axon repair. Despite growing research on H2O2 functions in wound repair, the downstream signaling pathways activated by this reactive oxygen species in the context of injury remain largely unknown. The goal of this study was to provide a comprehensive analysis of gene expression changes in the epidermis upon exposure to H2O2 concentrations known to promote wound repair. Comparative transcriptome analysis using RNA-seq data from larval zebrafish and previously reported microarray data from a human epidermal keratinocyte line shows that H2O2 activates conserved cell migration, adhesion, cytoprotective and anti-apoptotic programs in both zebrafish and human keratinocytes. Further assessment of expression characteristics and signaling pathways revealed the activation of three major H2O2-dependent pathways, EGF, FOXO1, and IKKα. This study expands on our current understanding of the clinical potential of low-level H2O2 for the promotion of epidermal wound repair and provides potential candidates in the treatment of wound healing deficits.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion / drug effects
  • Cell Line
  • Cell Movement / drug effects
  • Down-Regulation / drug effects
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / metabolism
  • Forkhead Box Protein O1 / genetics
  • Forkhead Box Protein O1 / metabolism
  • Gene Expression Profiling
  • Humans
  • Hydrogen Peroxide / toxicity*
  • Keratinocytes / cytology
  • Keratinocytes / metabolism
  • Larva / drug effects
  • Larva / growth & development
  • Larva / metabolism
  • NF-KappaB Inhibitor alpha / genetics
  • NF-KappaB Inhibitor alpha / metabolism
  • Real-Time Polymerase Chain Reaction
  • Sequence Analysis, RNA
  • Signal Transduction / drug effects*
  • Transcriptome / drug effects
  • Up-Regulation / drug effects
  • Wound Healing / drug effects*
  • Zebrafish / growth & development
  • Zebrafish / metabolism*


  • Forkhead Box Protein O1
  • NF-KappaB Inhibitor alpha
  • Epidermal Growth Factor
  • Hydrogen Peroxide