A potential wound healing-promoting peptide from frog skin

Int J Biochem Cell Biol. 2014 Apr:49:32-41. doi: 10.1016/j.biocel.2014.01.010. Epub 2014 Jan 17.

Abstract

Cutaneous wound healing is a dynamic, complex, and well-organized process that requires the orchestration of many different cell types and cellular processes. Transforming growth factor β1 is an important factor that plays a key role during wound healing. Amphibian skin has been proven to possess excellent wound healing ability, whilst no bioactive substrate related to it has ever been identified. Here, a potential wound healing-promoting peptide (AH90, ATAWDFGPHGLLPIRPIRIRPLCG) was identified from the frog skin of Odorrana grahami. It showed potential wound healing-promoting activity in a murine model with full thickness dermal wound. AH90 promoted release of transforming growth factor β1 through activation of nuclear factor-κB and c-Jun NH2-terminal kinase mitogen-activated protein kinases signaling pathways, while inhibitors of nuclear factor-κB and c-Jun NH2-terminal kinase inhibited the process. In addition, the effects of AH90 on Smads family proteins, key regulators in transforming growth factor β1 signaling pathways, could also be inhibited by transforming growth factor β1 antibody. Altogether, this indicated that AH90 promoted wound healing by inducing the release of transforming growth factor β1. This current study may facilitate the understanding of effective factors involved in the wound repair of amphibians and the underlying mechanisms as well. Considering its favorable traits as a small peptide that greatly promoting generation of endogenous wound healing agents (transforming growth factor β1) without mitogenic effects, AH90 might be an excellent template for the future development of novel wound-healing agents.

Keywords: Amphibian; Antimicrobial peptide; Transforming growth factor beta; Wound repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • Cell Adhesion / drug effects
  • Cell Line
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Dermis / drug effects
  • Dermis / metabolism
  • Dermis / physiopathology
  • Humans
  • Integrins / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • NF-kappa B / metabolism
  • Peptides / metabolism*
  • Peptides / pharmacology
  • Ranidae / metabolism*
  • Signal Transduction / drug effects
  • Skin / metabolism*
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta1 / metabolism
  • Wound Healing / drug effects
  • Wound Healing / physiology*

Substances

  • Integrins
  • NF-kappa B
  • Peptides
  • Smad3 Protein
  • Transforming Growth Factor beta1
  • JNK Mitogen-Activated Protein Kinases