title: 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.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Grazia
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Floriana
authors.initials: F
authors.lastname: Cappiello
authors.affiliation: Centre for Dermatology Research, Institute of Inflammation and Repair, University of Manchester, Manchester, United Kingdom.
authors.forename: Akiko
authors.initials: A
authors.lastname: Imanishi
authors.affiliation: Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, Rome, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Mastrofrancesco
authors.affiliation: Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Picardo
authors.affiliation: Centre for Dermatology Research, Institute of Inflammation and Repair, University of Manchester, Manchester, United Kingdom; Department of Dermatology, University of Münster, Münster, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
authors.affiliation: Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mangoni
mesh_terms: D029845:Amphibian Proteins / Q000494:pharmacology*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001001:Anura; D002460:Cell Line; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D017192:Skin Diseases, Bacterial / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D012883:Skin Ulcer / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects*; D054804:Cathelicidins
chemical_list: D029845:Amphibian Proteins; D023181:Antimicrobial Cationic Peptides; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C092874:esculentin protein, Rana esculenta; C512478:EGFR protein, human; D066246:ErbB Receptors; D054804:Cathelicidins