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.