title: The pro-healing effect of exendin-4 on wounds produced by abrasion in normoglycemic mice.
abstract: Experimental evidence suggested that Exendin-4 (Exe4), an agonist at glucagon like receptor-1 (GLP-1R), promoted tissue regeneration. We aimed to verify the effect of Exe4, in the absence or in the presence of Exendin-4(9-39), an antagonist at GLP-1R, on the healing of abraded skin. Two wounds (approximately 1.1×1.1 cm(2); namely "upper" and "lower" in respect of the head) were produced by abrasion on the back of 12 mice, which were then randomly assigned to receive an intradermal injection (20 μl) of Group 1: saline (NT) or Exe4 (62 ng) in the upper and lower wound respectively; Group 2: Exendin-4(9-39) (70 ng) in the upper and Exendin-4(9-39) (70 ng) and, after 15 min, Exe4 (62 ng) in the lower wound. Wounds were measured at the time of abrasion (T0) and 144 h (T3) afterward taking pictures with a ruler and by using a software. The inflammatory cell infiltrate, fibroblasts/myofibroblasts, endothelial cells and GLP-1R expression, were each labeled by immunofluorescence in each wound, pERK1/2 was evaluated by Western-blot in wound lysates. At T3, the percentage of healing surface was 53% and 92% for NT and Exe4 wounds respectively and 68% and 79% for those treated with Exendin-4(9-39) and Exendin-4(9-39)+Exe4 respectively. Exe4, but not Exendin-4(9-39) induced quantitative increase in fibroblasts/myofibroblasts and vessel density when compared to NT wounds. This increase was not evident in wounds treated with Exendin-4(9-39)+Exe4. Exe4 promotes wound healing opening to the possible dermatological use of this incretin analogue.
authors.affiliation: Department of Clinical and Experimental Medicine, Research Unit of Histology and Embriology, University of Florence, 50139 Florence, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bacci
authors.affiliation: Department of NEUROFARBA, Section of Pharmacology, University of Florence, 50139 Florence, Italy.
authors.forename: Annunziatina
authors.initials: A
authors.lastname: Laurino
authors.affiliation: Department of NEUROFARBA, Section of Pharmacology, University of Florence, 50139 Florence, Italy.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Manni
authors.affiliation: Department of Health Sciences, Section of Pharmacology, University of Florence, 50139 Florence, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Landucci
authors.affiliation: Department of NEUROFARBA, Section of Pharmacology, University of Florence, 50139 Florence, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Musilli
authors.affiliation: Department of Health Sciences, Section of Pharmacology, University of Florence, 50139 Florence, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: De Siena
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, Section of Experimental Pathology and Oncology, University of Florence, 50134 Florence, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mocali
authors.affiliation: Department of NEUROFARBA, Section of Pharmacology, University of Florence, 50139 Florence, Italy. Electronic address: laura.raimondi@unifi.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Raimondi
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D054338:Cell Transdifferentiation / Q000187:drug effects; D003879:Dermatologic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D000077270:Exenatide; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000067757:Glucagon-Like Peptide-1 Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism; D054795:Incretins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D058628:Myofibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation; D012867:Skin / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014688:Venoms / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D003879:Dermatologic Agents; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D010446:Peptide Fragments; D010455:Peptides; D014688:Venoms; C083773:exendin (9-39); D000077270:Exenatide; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: Angiogenesis; Exendin-4; Exendin-4(9-39); Glucagon-like type 1 receptor; Wound healing