title: Mutant matrix metalloproteinase-9 reduces postoperative peritoneal adhesions in rats.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Surgery, Faculty of Medicine, Minia University, Misr-Aswan Road, El-Minia 61519, Egypt. Electronic address: atta@mu.edu.eg.
authors.forename: Hussein
authors.initials: H
authors.lastname: Atta
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Minia University, Misr-Aswan Road, El-Minia 61519, Egypt. Electronic address: elrehany1963@yahoo.com.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: El-Rehany
authors.affiliation: Department of Gastroenterology, Justus-Liebig University Giessen, Germany. Electronic address: Elke.Roeb@innere.med.uni-giessen.de.
authors.forename: Elke
authors.initials: E
authors.lastname: Roeb
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Minia University, Misr-Aswan Road, El-Minia 61519, Egypt. Electronic address: hend.youssif@mu.edu.eg.
authors.forename: Hend
authors.initials: H
authors.lastname: Abdel-Ghany
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Minia University, Misr-Aswan Road, El-Minia 61519, Egypt. Electronic address: magymaher@mu.edu.eg.
authors.forename: Maggie
authors.initials: M
authors.lastname: Ramzy
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Minia University, Misr-Aswan Road, El-Minia 61519, Egypt. Electronic address: samy.shereen@yahoo.com.
authors.forename: Shereen
authors.initials: S
authors.lastname: Gaber
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D050505:Mutant Proteins / Q000235:genetics*; D010532:Peritoneal Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011183:Postoperative Complications / Q000517:prevention & control; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D000267:Tissue Adhesions / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D050505:Mutant Proteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D010959:Tissue Plasminogen Activator; D020780:Matrix Metalloproteinase 9
keywords: Adenovirus gene therapy; Matrix metalloproteinase-9; Peritoneal adhesions; Plasminogen activator inhibitor-1; Tissue plasminogen activator; Transforming growth factor beta-1