1. Mutant matrix metalloproteinase-9 reduces postoperative peritoneal adhesions in rats.
- Author
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Atta H, El-Rehany M, Roeb E, Abdel-Ghany H, Ramzy M, and Gaber S
- Subjects
- Adenoviridae genetics, Animals, Genetic Vectors genetics, Peritoneal Diseases metabolism, Peritoneal Diseases pathology, Plasminogen Activator Inhibitor 1 metabolism, Postoperative Complications prevention & control, RNA, Messenger metabolism, Rats, Wistar, Tissue Adhesions metabolism, Tissue Adhesions pathology, Tissue Plasminogen Activator metabolism, Transforming Growth Factor beta1 metabolism, Genetic Therapy methods, Matrix Metalloproteinase 9 genetics, Mutant Proteins genetics, Peritoneal Diseases prevention & control, Tissue Adhesions prevention & control
- Abstract
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., (Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2016
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