title: 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 60μg/wound pcDNA3-FLAG-SPK1 (P<0.001-0.01). The mean sizes of the wounds were 0.67±0.15cm(2), 0.83±0.18cm(2), and 1.09±0.23cm(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 60μg/wound respectively, and 55.4±9.9% in diabetic control group (P<0.001-0.01). Histology revealed that tissue sections from the treated diabetic rats contained more granulation tissue and capillaries than that of the control rats. There was high SPK1 expression in the skin of the treated diabetic rats.
  
  
  CONCLUSIONS
  SPK1 gene therapy may represent a novel approach to cutaneous wound healing.
authors.affiliation: Beijing Institute of Radiation Medicine (BIRM), No. 27, Taiping Road, Beijing 100850, Haidian District, China; Beijing Institute of Pharmacology and Toxicology, No. 27, Taiping Road, Beijing 100850, Haidian District, China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Yu
authors.affiliation: Beijing Institute of Radiation Medicine (BIRM), No. 27, Taiping Road, Beijing 100850, Haidian District, China.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Beijing Shuanglu Pharmaceutical Company, No. 69, Fushi Road, Beijing 100049, Haidian District, China.
authors.forename: Mingbo
authors.initials: M
authors.lastname: Xu
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, No. 27, Taiping Road, Beijing 100850, Haidian District, China.
authors.forename: Zhenqing
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Radiation Medicine (BIRM), No. 27, Taiping Road, Beijing 100850, Haidian District, China. Electronic address: 15811571889@163.com.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Duan
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D048909:Diabetes Complications / Q000188:drug therapy / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D008246:Lysophospholipids / Q000494:pharmacology*; D008297:Male; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000473:pathology / Q000503:physiopathology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*; D000099157:Sphingosine Kinase
chemical_list: D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate
keywords: Diabetic rats; Diabetic wound healing; Sphingosine kinase 1