Non-viral Smad7 gene delivery and attenuation of postoperative peritoneal adhesion in an experimental model

Background: Postoperative intra‐abdominal adhesion is associated with high morbidity and mortality. Smad7, a protein that occupies a strategic position in fibrogenesis, inhibits the transforming growth factor (TGF) β/Smad signalling pathway. In this study the therapeutic potential of exogenous Smad7 in preventing fibrogenesis in postoperative intra‐abdominal adhesion was investigated. Methods: Intra‐abdominal adhesion was induced in a rodent model by peritoneal abrasion. Smad7 was delivered into the peritoneal cavity by a non‐viral ultrasound–microbubble‐mediated naked gene transfection system. The effect of Smad7 transgene on adhesion formation was studied by measuring changes in TGF‐β, fibrogenic factors, α‐SMA and Smad2/3 activation in the anterior abdominal wall. Results: Four weeks after surgical abrasion, all rats developed significant peritoneal adhesion with enhanced TGF‐β expression, increased levels of extracellular matrix components and activated myofibroblasts, accompanied by decreased Smad7 expression and increased Smad2/3 activation. In rats treated with the Smad7 transgene, the incidence and severity of peritoneal adhesion were significantly reduced, with biochemical downregulation of fibrogenic factors and inhibition of Smad2/3 activation. Serial quantitation using magnetic resonance imaging revealed a significant reduction in adhesion areas from day 14 onwards. Conclusion: Ultrasound–microbubble‐mediated gene transfection provides timely targeted gene delivery for the treatment of postoperative peritoneal adhesions. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. Another possibility for gene therapy