Journalartikel

Mutant matrix metalloproteinase-9 reduces postoperative peritoneal adhesions in rats


AutorenlisteAtta, Hussein; El-Rehany, Mahmoud; Roeb, Elke; Abdel-Ghany, Hend; Ramzy, Maggie; Gaber, Shereen

Jahr der Veröffentlichung2016

Seiten58-63

ZeitschriftInternational Journal of Surgery

Bandnummer26

ISSN1743-9191

eISSN1743-9159

Open Access StatusBronze

DOI Linkhttps://doi.org/10.1016/j.ijsu.2015.12.065

VerlagElsevier


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.




Zitierstile

Harvard-ZitierstilAtta, 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-ZitierstilAtta, 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



Schlagwörter


Adenovirus gene therapyFibrinolysisINTRAPERITONEAL ORGANSMatrix metalloproteinase-9MATRIX-METALLOPROTEINASE MMP-1Peritoneal adhesionsTISSUE-PLASMINOGEN ACTIVATORTransforming growth factor beta-1TRANSFORMING GROWTH-FACTOR-BETA-1


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