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Int J Surg. 2016 Feb;26:58-63. doi: 10.1016/j.ijsu.2015.12.065. Epub 2016 Jan 12.

Mutant matrix metalloproteinase-9 reduces postoperative peritoneal adhesions in rats.

Author information

1
Department of Surgery, Faculty of Medicine, Minia University, Misr-Aswan Road, El-Minia 61519, Egypt. Electronic address: atta@mu.edu.eg.
2
Department of Biochemistry, Faculty of Medicine, Minia University, Misr-Aswan Road, El-Minia 61519, Egypt. Electronic address: elrehany1963@yahoo.com.
3
Department of Gastroenterology, Justus-Liebig University Giessen, Germany. Electronic address: Elke.Roeb@innere.med.uni-giessen.de.
4
Department of Biochemistry, Faculty of Medicine, Minia University, Misr-Aswan Road, El-Minia 61519, Egypt. Electronic address: hend.youssif@mu.edu.eg.
5
Department of Biochemistry, Faculty of Medicine, Minia University, Misr-Aswan Road, El-Minia 61519, Egypt. Electronic address: magymaher@mu.edu.eg.
6
Department of Biochemistry, Faculty of Medicine, Minia University, Misr-Aswan Road, El-Minia 61519, Egypt. Electronic address: samy.shereen@yahoo.com.

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.

KEYWORDS:

Adenovirus gene therapy; Matrix metalloproteinase-9; Peritoneal adhesions; Plasminogen activator inhibitor-1; Tissue plasminogen activator; Transforming growth factor beta-1

PMID:
26790972
DOI:
10.1016/j.ijsu.2015.12.065
[Indexed for MEDLINE]
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