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Updated: Mar 26, 2026
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Published on: August 27, 2016
Mutant matrix metalloproteinase-9 reduces postoperative peritoneal adhesions in rats
Hussein Atta1, Mahmoud El-Rehany2, Elke Roeb3
1Department of Surgery, Faculty of Medicine, Minia University, Misr-Aswan Road, El-Minia 61519, Egypt.
Introduction:
Postoperative peritoneal adhesions continue to be a major source of morbidity and occasional mortality. Studies have shown that matrix metalloproteinase-9 (MMP-9) levels are decreased postoperatively which may limits matrix degradation and participate in the development of peritoneal adhesions. In this proof-of-principle study, we evaluated the effect of gene therapy with catalytically inactive mutant MMP-9 on postoperative peritoneal adhesions in rats.
Methods:
Adenovirus encoding mutant MMP-9 (Ad-mMMP-9) or saline was instilled in the peritoneal cavity after cecal and parietal peritoneal injury in rats. Expression of mutant MMP-9 transcript was verified by sequencing. Adenovirus E4 gene expression, adhesion scores, MMP-9, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor-β1 (TGF-β1) expression were evaluated at sacrifice one week after treatment.
Results:
Both mutant MMP-9 transcripts and adenovirus E4 gene were expressed in Ad-mMMP-9 treated adhesions. Adhesions severity decreased significantly (p = 0.036) in the Ad-mMMP-9-treated compared with saline-treated adhesions. Expression of MMP-9 mRNA and protein were elevated (p = 0.001 and p = 0.029, respectively) in the Ad-mMMP-9-treated adhesions compared with saline-treated adhesions. While tPA levels were increased (p = 0.02) in Ad-mMMP-9 treated adhesions compared with saline-treated adhesions, TGF-β1 and PAI-1 levels were decreased (p = 0.017 and p = 0.042, respectively). No difference in mortality were found between groups (p = 0.64).
Conclusions:
Mutant MMP-9 gene therapy effectively transduced peritoneal adhesions resulting in reduction of severity of primary peritoneal adhesions.
Insights
Gene therapy using mutant matrix metalloproteinase-9 (MMP-9) effectively reduced postoperative peritoneal adhesions in rats. This approach shows promise for preventing adhesion formation and improving patient outcomes.
Area of Science:
- Molecular biology
- Gene therapy
- Surgical research
Background:
- Postoperative peritoneal adhesions cause significant morbidity.
- Reduced matrix metalloproteinase-9 (MMP-9) levels may contribute to adhesion development.
- This study investigates gene therapy for preventing adhesions.
Purpose of the Study:
- To evaluate the efficacy of gene therapy with a catalytically inactive mutant MMP-9 (Ad-mMMP-9) in reducing postoperative peritoneal adhesions in a rat model.
Main Methods:
- Rats received Ad-mMMP-9 or saline after peritoneal injury.
- Mutant MMP-9 gene expression was confirmed.
- Adhesion scores and expression of MMP-9, tPA, PAI-1, and TGF-β1 were assessed.
Main Results:
- Ad-mMMP-9 treatment significantly reduced adhesion severity (p=0.036).
- MMP-9 expression increased, while TGF-β1 and PAI-1 decreased in treated adhesions.
- Tissue plasminogen activator (tPA) levels were elevated post-treatment.
Conclusions:
- Mutant MMP-9 gene therapy successfully transduced peritoneal adhesions.
- This gene therapy approach effectively reduced the severity of primary peritoneal adhesions.
