title: Epoetin Alpha and Epoetin Zeta: A Comparative Study on Stimulation of Angiogenesis and Wound Repair in an Experimental Model of Burn Injury.
abstract: Deep second-degree burns are characterized by delayed formation of granulation tissue and impaired angiogenesis. Erythropoietin (EPO) is able to stimulate angiogenesis and mitosis, activating vascularization and cell cycle. The aim of our study was to investigate whether two biosimilar recombinant human erythropoietins, EPO-α and EPO-Z, may promote these processes in an experimental model of burn injury. A total of 84 mice were used and a scald burn was produced on the back after shaving, in 80°C water for 10 seconds. Mice were then randomized to receive EPO-α (400 units/kg/day/sc) or EPO-Z (400 units/kg/day/sc) or their vehicle (100 μL/day/sc 0.9% NaCl solution). After 12 days, both EPO-α and EPO-Z increased VEGF protein expression. EPO-α caused an increased cyclin D1/CDK6 and cyclin E/CDK2 expression compared with vehicle and EPO-Z (p<0.001). Our study showed that EPO-α and EPO-Z accelerated wound closure and angiogenesis; however EPO-α resulted more effectively in achieving complete skin regeneration. Our data suggest that EPO-α and EPO-Z are not biosimilars for the wound healing effects. The higher efficacy of EPO-α might be likely due to its different conformational structure leading to a more efficient cell proliferation and skin remodelling.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.
authors.forename: Natasha
authors.initials: N
authors.lastname: Irrera
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pizzino
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Vaccaro
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
authors.affiliation: Department of Dentistry and Medical and Surgical Experimental Sciences, University of Messina, 98125 Messina, Italy.
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Galeano
authors.affiliation: Department of Dentistry and Medical and Surgical Experimental Sciences, University of Messina, 98125 Messina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Stagno d'Alcontres
authors.affiliation: Department of Dentistry and Medical and Surgical Experimental Sciences, University of Messina, 98125 Messina, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Stagno d'Alcontres
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Buemi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy.
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.affiliation: Department of Dentistry and Medical and Surgical Experimental Sciences, University of Messina, 98125 Messina, Italy.
authors.forename: Michele Rosario
authors.initials: MR
authors.lastname: Colonna
authors.affiliation: Department of Paediatric, Gynaecological, Microbiological and Biomedical Sciences, University of Messina, 98125 Messina, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000235:genetics; D002056:Burns / Q000188:drug therapy / Q000503:physiopathology; D000068817:Epoetin Alfa / Q000008:administration & dosage* / Q000235:genetics; D004921:Erythropoietin / Q000008:administration & dosage* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D008962:Models, Theoretical; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics*; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics
chemical_list: D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C530192:epoetin zeta; C467480:vascular endothelial growth factor A, mouse; D004921:Erythropoietin; D000068817:Epoetin Alfa