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Non-viral Smad7 gene delivery and attenuation of postoperative peritoneal adhesion in an experimental model
H Guo1, J C K Leung, J S Cheung
1Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong.
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) beta/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-beta, fibrogenic factors, alpha-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-beta 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.
Insights
Smad7 gene therapy effectively reduced postoperative intra-abdominal adhesions in a rodent model. This approach targets fibrogenesis by inhibiting transforming growth factor-beta signaling, offering a promising treatment for adhesion prevention.
Area of Science:
- Regenerative Medicine
- Molecular Biology
- Surgical Innovation
Background:
- Postoperative intra-abdominal adhesions cause significant morbidity and mortality.
- Smad7 protein inhibits fibrogenesis by blocking the transforming growth factor (TGF)-beta/Smad signaling pathway.
Purpose of the Study:
- To investigate the therapeutic potential of exogenous Smad7 in preventing fibrogenesis in postoperative intra-abdominal adhesions.
Main Methods:
- Intra-abdominal adhesions were induced in a rodent model via peritoneal abrasion.
- Smad7 gene was delivered using ultrasound-microbubble-mediated naked gene transfection.
- Effects were assessed by measuring TGF-beta, fibrogenic factors, alpha-SMA, and Smad2/3 activation.
Main Results:
- Smad7 transgene treatment significantly reduced adhesion incidence and severity.
- Biochemical analysis showed downregulation of fibrogenic factors and inhibited Smad2/3 activation.
- Magnetic resonance imaging confirmed a significant reduction in adhesion areas from day 14.
Conclusions:
- Ultrasound-microbubble-mediated gene transfection enables targeted Smad7 delivery for treating postoperative peritoneal adhesions.
- This method shows promise for preventing and managing intra-abdominal adhesions.
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