Sphingosine kinase 1 gene transfer reduces postoperative peritoneal adhesion in an experimental model.
BACKGROUND
Recovery of the surgically damaged mesothelial cell layer is a major process in reducing postoperative peritoneal adhesions. Sphingosine kinase (SPK) 1 is a signalling molecule involved in the regulation of proliferation and migration of various cell types. This study determined the effect of SPK-1 gene transfer on the recovery of damaged mesothelial cells and on peritoneal adhesion formation after surgery.


METHODS
Rat mesothelial cells were isolated and characterized by their expression of cytokeratin and vimentin. Their migration was determined by scratch wound motility assay. Cellular SPK-1 activity was measured by [gamma-32P]adenosine 5'-triphosphate incorporation. Wistar rats underwent laparotomy with subsequent caecum or uterine horn abrasion. Rats were randomized to either SPK-1 gene (Ad-SPK-1) transfer or control groups. The animals were killed 14 days after operation and peritoneal adhesions were graded.


RESULTS
Adenovirus-mediated SPK-1 gene transfer increased the cellular SPK-1 activity of mesothelial cells, leading to enhanced migration. Median adhesion scores were significantly lower in the Ad-SPK-1 group than in controls in both rat caecum (0.98 versus 2.60; P < 0.001) and rat uterine horn (0.28 versus 1.83; P < 0.001) models.


CONCLUSIONS
Adenovirus-mediated SPK-1 gene transfer promotes recovery of the surgically damaged mesothelial cell layer and prevents postoperative peritoneal adhesion formation.
Guo
Q
Q
Department of General Surgery, General Hospital of People's Liberation Army, Beijing Institute of Radiation Medicine, Beijing, China.
Li
Q-F
QF
Liu
H-J
HJ
Li
R
R
Wu
C-T
CT
Wang
L-S
LS
D000256:Adenoviridae; D000818:Animals; D015153:Blotting, Western; D002432:Cecum / Q000601:surgery; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D018014:Gene Transfer Techniques; D010532:Peritoneal Diseases / Q000473:pathology / Q000517:prevention & control*; D010537:Peritoneum / Q000601:surgery*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics* / Q000378:metabolism; D011184:Postoperative Period; D051381:Rats; D017208:Rats, Wistar; D000267:Tissue Adhesions / Q000473:pathology / Q000517:prevention & control; D014599:Uterus / Q000601:surgery; D000099157:Sphingosine Kinase
D017853:Phosphotransferases (Alcohol Group Acceptor); D000099157:Sphingosine Kinase