Sphingosine kinase 1 improves cutaneous wound healing in diabetic rats

Abstract Background Diabetes is one of the most prevalent human metabolic diseases. Wound healing in diabetes is frequently impaired and treatment remains challenging. Sphingolipid metabolites play important roles in the regulation of glucose metabolism. SPK1 is the key enzyme in the sphingolipid metabolic pathway. S1P/SPK plays a pivotal role in the signalling pathways of diverse cellular processes including proliferation, differentiation, migration, apoptosis in diverse cell types. Methods To investigate the role of sphingosine kinase 1 (SPK1) in skin injury, plasmids containing the SPK1 gene (pcDNA3-FLAG-SPK1) were applied to cutaneous wounds on a streptozotocin-induced diabetic rat model over a 21-day period. The wound area and rate of wound healing were determined. The histopathological features of the healed wounds were also observed, and SPK1 expression in the skin was detected by immunohistochemistry. Results There was a significant decrease in wound area in diabetic rats treated with 125 and 60 μg/wound pcDNA3-FLAG-SPK1 ( P 2 , 0.83 ± 0.18 cm 2 , and 1.09 ± 0.23 cm 2 in both treated and diabetic control group at the 7th day post-treatment respectively. In addition, wound healing in diabetic rats of test group was accelerated. At the 7th day, the mean rates of healing were 73.2 ± 5.7% and 66 ± 7.3% in test group of 125 and 60 μg/wound respectively, and 55.4 ± 9.9% in diabetic control group ( P Conclusions SPK1 gene therapy may represent a novel approach to cutaneous wound healing.