title: Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse.
abstract: Healing of diabetic wounds still remains a critical medical problem. Polydeoxyribonucleotide (PDRN), a compound having a mixture of deoxyribonucleotide polymers, stimulates the A2 purinergic receptor with no toxic or adverse effect. We studied the effects of PDRN in diabetes-related healing defect using an incisional skin-wound model produced on the back of female diabetic mice (db+/db+) and their normal littermates (db+/+m). Animals were treated daily for 12 days with PDRN (8 mg/kg/ip) or its vehicle (100 muL 0.9%NaCl). Mice were killed 3, 6, and 12 days after skin injury to measure vascular endothelial growth factor (VEGF) mRNA expression and protein synthesis, to assay angiogenesis and tissue remodeling through histological evaluation, and to study CD31, Angiopoietin-1 and Transglutaminase-II. Furthermore, we measured wound breaking strength at day 12. PDRN injection in diabetic mice resulted in an increased VEGF message (vehicle=1.0+/-0.2 n-fold vs. beta-actin; PDRN=1.5+/-0.09 n-fold vs. beta-actin) and protein wound content on day 6 (vehicle=0.3+/-0.07 pg/wound; PDRN=0.9+/-0.1 pg/wound). PDRN injection improved the impaired wound healing and increased the wound-breaking strength in diabetic mice. PDRN also caused a marked increase in CD31 immunostaining and induced Transglutaminase-II and Angiopoietin-1 expression. Furthermore, the concomitant administration of 3,7-dimethyl-1-propargilxanthine, a selective adenosine A2A receptor antagonist, abolished PDRN positive effects on healing. However, 3,7-dimethyl-1-propargilxanthine alone did not affect wound healing in both diabetic mice and normal littermates. These results suggest that PDRN might be useful in wound disorders associated with diabetes.
authors.affiliation: Department of Surgical Sciences, Section of Plastic Surgery, Messina, Italy.
authors.forename: Mariarosaria
authors.initials: M
authors.lastname: Galeano
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.forename: Francesca
authors.initials: F
authors.lastname: Polito
authors.forename: Margherita
authors.initials: M
authors.lastname: Calò
authors.forename: Patrizia
authors.initials: P
authors.lastname: Lo Cascio
authors.forename: Francesco
authors.initials: F
authors.lastname: Stagno d'Alcontres
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D042683:Angiopoietin-1 / Q000378:metabolism; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011089:Polydeoxyribonucleotides / Q000494:pharmacology*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; D018952:Antigens, CD34; D011089:Polydeoxyribonucleotides; D042461:Vascular Endothelial Growth Factor A; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins