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

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 die 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 [γ-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. Copyright © 2008 British Journal of Surgery Society Ltd.