Journal article

Publication year: 2016

Pages: 58-63

Journal: International Journal of Surgery

Volume number: 26

ISSN: 1743-9191

eISSN: 1743-9159

Open access status: Bronze

DOI Link: https://doi.org/10.1016/j.ijsu.2015.12.065

Publisher: Elsevier

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-beta 1 (TGF-beta 1) 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-beta 1 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. (c) 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Harvard Citation style: Atta, H., El-Rehany, M., Roeb, E., Abdel-Ghany, H., Ramzy, M. and Gaber, S. (2016) Mutant matrix metalloproteinase-9 reduces postoperative peritoneal adhesions in rats, International Journal of Surgery, 26, pp. 58-63. https://doi.org/10.1016/j.ijsu.2015.12.065

APA Citation style: Atta, H., El-Rehany, M., Roeb, E., Abdel-Ghany, H., Ramzy, M., & Gaber, S. (2016). Mutant matrix metalloproteinase-9 reduces postoperative peritoneal adhesions in rats. International Journal of Surgery. 26, 58-63. https://doi.org/10.1016/j.ijsu.2015.12.065