The Frog Skin-Derived Antimicrobial Peptide Esculentin-1a(1-21)NH2 Promotes the Migration of Human HaCaT Keratinocytes in an EGF Receptor-Dependent Manner: A Novel Promoter of Human Skin Wound Healing?

Abstract

One of the many functions of skin is to protect the organism against a wide range of pathogens. Antimicrobial peptides (AMPs) produced by the skin epithelium provide an effective chemical shield against microbial pathogens. However, whereas antibacterial/antifungal activities of AMPs have been extensively characterized, much less is known regarding their wound healing-modulatory properties. By using an in vitro re-epithelialisation assay employing special cell-culture inserts, we detected that a derivative of the frog-skin AMP esculentin-1a, named esculentin-1a(1-21)NH2, significantly stimulates migration of immortalized human keratinocytes (HaCaT cells) over a wide range of peptide concentrations (0.025-4 μM), and this notably more efficiently than human cathelicidin (LL-37). This activity is preserved in primary human epidermal keratinocytes. By using appropriate inhibitors and an enzyme-linked immunosorbent assay we found that the peptide-induced cell migration involves activation of the epidermal growth factor receptor and STAT3 protein. These results suggest that esculentin-1a(1-21)NH2 now deserves to be tested in standard wound healing assays as a novel candidate promoter of skin re-epithelialisation. The established ability of esculentin-1a(1-21)NH2 to kill microbes without harming mammalian cells, namely its high anti-Pseudomonal activity, makes this AMP a particularly attractive candidate wound healing promoter, especially in the management of chronic, often Pseudomonas-infected, skin ulcers.

• Authors: Antonio Di Grazia, Floriana Cappiello, Akiko Imanishi, Arianna Mastrofrancesco, Mauro Picardo, Ralf Paus, Maria Luisa Mangoni
• Journal: PloS one (PLoS One) Vol. 10 Issue 6 Pg. e0128663 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26068861 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amphibian Proteins
• Antimicrobial Cationic Peptides
• STAT3 Transcription Factor
• STAT3 protein, human
• esculentin protein, Rana esculenta
• EGFR protein, human
• ErbB Receptors
• Cathelicidins

Topics

• Amphibian Proteins (pharmacology)
• Animals
• Antimicrobial Cationic Peptides (pharmacology)
• Anura
• Cell Line
• ErbB Receptors (metabolism)
• Humans
• Keratinocytes (metabolism, pathology)
• Pseudomonas Infections (drug therapy, metabolism, pathology)
• STAT3 Transcription Factor (metabolism)
• Skin (metabolism, pathology)
• Skin Diseases, Bacterial (drug therapy, metabolism, pathology)
• Skin Ulcer (drug therapy, metabolism, pathology)
• Wound Healing (drug effects)
• Cathelicidins