Sphingosine kinase 1 gene transfer reduces postoperative peritoneal adhesion in an experimental model

Br J Surg. 2008 Feb;95(2):252-8. doi: 10.1002/bjs.5890.

Abstract

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.

Conclusion: Adenovirus-mediated SPK-1 gene transfer promotes recovery of the surgically damaged mesothelial cell layer and prevents postoperative peritoneal adhesion formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae
  • Animals
  • Blotting, Western
  • Cecum / surgery
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Gene Transfer Techniques*
  • Peritoneal Diseases / pathology
  • Peritoneal Diseases / prevention & control*
  • Peritoneum / surgery*
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Postoperative Period
  • Rats
  • Rats, Wistar
  • Tissue Adhesions / pathology
  • Tissue Adhesions / prevention & control
  • Uterus / surgery

Substances

  • Phosphotransferases (Alcohol Group Acceptor)
  • sphingosine kinase