A potential wound-healing-promoting peptide from salamander skin

FASEB J. 2014 Sep;28(9):3919-29. doi: 10.1096/fj.13-248476. Epub 2014 May 27.

Abstract

Although it is well known that wound healing proceeds incredibly quickly in urodele amphibians, such as newts and salamanders, little is known about skin-wound healing, and no bioactive/effector substance that contributes to wound healing has been identified from these animals. As a step toward understanding salamander wound healing and skin regeneration, a potential wound-healing-promoting peptide (tylotoin; KCVRQNNKRVCK) was identified from salamander skin of Tylototriton verrucosus. It shows comparable wound-healing-promoting ability (EC50=11.14 μg/ml) with epidermal growth factor (EGF; NSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCQYRDLKWWELR) in a murine model of full-thickness dermal wound. Tylotoin directly enhances the motility and proliferation of keratinocytes, vascular endothelial cells, and fibroblasts, resulting in accelerated reepithelialization and granulation tissue formation in the wound site. Tylotoin also promotes the release of transforming growth factor β1 (TGF-β1) and interleukin 6 (IL-6), which are essential in the wound healing response. Gene-encoded tylotoin secreted in salamander skin is possibly an effector molecule for skin wound healing. This study may facilitate understanding of the cellular and molecular events that underlie quick wound healing in salamanders.

Keywords: TGF-β; full-thickness incision; reepithelialization; urodele amphibians.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Enzyme-Linked Immunosorbent Assay
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Flow Cytometry
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Immunoenzyme Techniques
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Peptide Fragments / chemistry
  • Peptide Fragments / isolation & purification*
  • Peptide Fragments / pharmacology*
  • RNA, Messenger / genetics
  • Rats
  • Real-Time Polymerase Chain Reaction
  • Regeneration / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / growth & development
  • Skin / metabolism*
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism
  • Urodela / growth & development
  • Urodela / metabolism*
  • Wound Healing / drug effects
  • Wound Healing / physiology*

Substances

  • Interleukin-6
  • Peptide Fragments
  • RNA, Messenger
  • Transforming Growth Factor beta1