Modified Adenovirus Reduces De Novo Peritoneal Adhesions in Rats and Limits Off-Target Transfection. Role of EZH2 in Adhesion Formation

Hussein M. Atta, Ayman A. Al-Hendy, Salama R. Abdel Raheim, Hend Abdel-Ghany, Khalid A. Nasif, Ahlam M. Abdellah, Nagwa M. Zenhom, Heba S. Kamel

Research output: Contribution to journalArticle

Abstract

Aim of the study: Adenovector encoding tissue plasminogen activator (tPA) was shown to reduce experimental peritoneal adhesion. We investigated the targeting potential of our modified adenovector, its ability to reduce adhesions and the epigenetic role of histone methyltransferase EZH2 in adhesion formation. Materials and methods: Control lacZ, nonmodified tPA or modified tPA vectors were instilled in the peritoneal cavity after injury in de novo adhesions or after lysis of adhesions in recurrent adhesions. Adhesion severity was scored and adhesions and liver tissues were examined for adenovirus E4 gene and tPA mRNA expression. Levels of tPA, plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-β1 (TGF-β1), and EZH2 expression were measured. Results: E4 transcripts were detected in adhesions of nonmodified and modified and in livers of nonmodified but not in livers of modified de novo adhesions. Both nonmodified (p = 0.021) and modified vectors (p = 0.036) reduced the severity of de novo adhesions compared to lacZ vector. Levels of tPA in nonmodified (p = 0.021) and modified adhesions (p = 0.001) were elevated while PAI-1 (p = 0.013 and p = 0.001, respectively) and TGF-β1 levels (p = 0.002 and p = 0.016, respectively) were reduced compared with lacZ group. All vectors were not expressed in recurrent adhesions and severity score were not different among groups. EZH2 levels were elevated in de novo nontreated (p = 0.001) and was further increased in recurrent (p = 0.001) nontreated adhesions compared with noninjured peritoneum. Conclusion: Modified adenovirus successfully targeted de novo adhesions but not liver tissues and reduced the severity of de novo adhesions. EZH2 is involved in the development and progression of peritoneal adhesions.

Original languageEnglish (US)
Pages (from-to)78-87
Number of pages10
JournalJournal of Investigative Surgery
Volume30
Issue number2
DOIs
StatePublished - Mar 4 2017

Fingerprint

Tissue Plasminogen Activator
Adenoviridae
Transfection
Liver
Plasminogen Activator Inhibitor 1
Transforming Growth Factors
Tissue Adhesions
Peritoneum
Peritoneal Cavity
Epigenomics
Messenger RNA
Wounds and Injuries
Genes

Keywords

  • gene therapy
  • histone methyltransferase
  • peritoneal adhesions
  • plasminogen activator inhibitor-1
  • tissue plasminogen activator
  • transforming growth factor beta-1

ASJC Scopus subject areas

  • Surgery

Cite this

Atta, H. M., Al-Hendy, A. A., Abdel Raheim, S. R., Abdel-Ghany, H., Nasif, K. A., Abdellah, A. M., ... Kamel, H. S. (2017). Modified Adenovirus Reduces De Novo Peritoneal Adhesions in Rats and Limits Off-Target Transfection. Role of EZH2 in Adhesion Formation. Journal of Investigative Surgery, 30(2), 78-87. https://doi.org/10.1080/08941939.2016.1229366

Modified Adenovirus Reduces De Novo Peritoneal Adhesions in Rats and Limits Off-Target Transfection. Role of EZH2 in Adhesion Formation. / Atta, Hussein M.; Al-Hendy, Ayman A.; Abdel Raheim, Salama R.; Abdel-Ghany, Hend; Nasif, Khalid A.; Abdellah, Ahlam M.; Zenhom, Nagwa M.; Kamel, Heba S.

In: Journal of Investigative Surgery, Vol. 30, No. 2, 04.03.2017, p. 78-87.

Research output: Contribution to journalArticle

Atta, HM, Al-Hendy, AA, Abdel Raheim, SR, Abdel-Ghany, H, Nasif, KA, Abdellah, AM, Zenhom, NM & Kamel, HS 2017, 'Modified Adenovirus Reduces De Novo Peritoneal Adhesions in Rats and Limits Off-Target Transfection. Role of EZH2 in Adhesion Formation', Journal of Investigative Surgery, vol. 30, no. 2, pp. 78-87. https://doi.org/10.1080/08941939.2016.1229366
Atta, Hussein M. ; Al-Hendy, Ayman A. ; Abdel Raheim, Salama R. ; Abdel-Ghany, Hend ; Nasif, Khalid A. ; Abdellah, Ahlam M. ; Zenhom, Nagwa M. ; Kamel, Heba S. / Modified Adenovirus Reduces De Novo Peritoneal Adhesions in Rats and Limits Off-Target Transfection. Role of EZH2 in Adhesion Formation. In: Journal of Investigative Surgery. 2017 ; Vol. 30, No. 2. pp. 78-87.
@article{6ce41079b22a46489e9bdfd61943588a,
title = "Modified Adenovirus Reduces De Novo Peritoneal Adhesions in Rats and Limits Off-Target Transfection. Role of EZH2 in Adhesion Formation",
abstract = "Aim of the study: Adenovector encoding tissue plasminogen activator (tPA) was shown to reduce experimental peritoneal adhesion. We investigated the targeting potential of our modified adenovector, its ability to reduce adhesions and the epigenetic role of histone methyltransferase EZH2 in adhesion formation. Materials and methods: Control lacZ, nonmodified tPA or modified tPA vectors were instilled in the peritoneal cavity after injury in de novo adhesions or after lysis of adhesions in recurrent adhesions. Adhesion severity was scored and adhesions and liver tissues were examined for adenovirus E4 gene and tPA mRNA expression. Levels of tPA, plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-β1 (TGF-β1), and EZH2 expression were measured. Results: E4 transcripts were detected in adhesions of nonmodified and modified and in livers of nonmodified but not in livers of modified de novo adhesions. Both nonmodified (p = 0.021) and modified vectors (p = 0.036) reduced the severity of de novo adhesions compared to lacZ vector. Levels of tPA in nonmodified (p = 0.021) and modified adhesions (p = 0.001) were elevated while PAI-1 (p = 0.013 and p = 0.001, respectively) and TGF-β1 levels (p = 0.002 and p = 0.016, respectively) were reduced compared with lacZ group. All vectors were not expressed in recurrent adhesions and severity score were not different among groups. EZH2 levels were elevated in de novo nontreated (p = 0.001) and was further increased in recurrent (p = 0.001) nontreated adhesions compared with noninjured peritoneum. Conclusion: Modified adenovirus successfully targeted de novo adhesions but not liver tissues and reduced the severity of de novo adhesions. EZH2 is involved in the development and progression of peritoneal adhesions.",
keywords = "gene therapy, histone methyltransferase, peritoneal adhesions, plasminogen activator inhibitor-1, tissue plasminogen activator, transforming growth factor beta-1",
author = "Atta, {Hussein M.} and Al-Hendy, {Ayman A.} and {Abdel Raheim}, {Salama R.} and Hend Abdel-Ghany and Nasif, {Khalid A.} and Abdellah, {Ahlam M.} and Zenhom, {Nagwa M.} and Kamel, {Heba S.}",
year = "2017",
month = "3",
day = "4",
doi = "10.1080/08941939.2016.1229366",
language = "English (US)",
volume = "30",
pages = "78--87",
journal = "Journal of Investigative Surgery",
issn = "0894-1939",
publisher = "Informa Healthcare",
number = "2",

}

TY - JOUR

T1 - Modified Adenovirus Reduces De Novo Peritoneal Adhesions in Rats and Limits Off-Target Transfection. Role of EZH2 in Adhesion Formation

AU - Atta, Hussein M.

AU - Al-Hendy, Ayman A.

AU - Abdel Raheim, Salama R.

AU - Abdel-Ghany, Hend

AU - Nasif, Khalid A.

AU - Abdellah, Ahlam M.

AU - Zenhom, Nagwa M.

AU - Kamel, Heba S.

PY - 2017/3/4

Y1 - 2017/3/4

N2 - Aim of the study: Adenovector encoding tissue plasminogen activator (tPA) was shown to reduce experimental peritoneal adhesion. We investigated the targeting potential of our modified adenovector, its ability to reduce adhesions and the epigenetic role of histone methyltransferase EZH2 in adhesion formation. Materials and methods: Control lacZ, nonmodified tPA or modified tPA vectors were instilled in the peritoneal cavity after injury in de novo adhesions or after lysis of adhesions in recurrent adhesions. Adhesion severity was scored and adhesions and liver tissues were examined for adenovirus E4 gene and tPA mRNA expression. Levels of tPA, plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-β1 (TGF-β1), and EZH2 expression were measured. Results: E4 transcripts were detected in adhesions of nonmodified and modified and in livers of nonmodified but not in livers of modified de novo adhesions. Both nonmodified (p = 0.021) and modified vectors (p = 0.036) reduced the severity of de novo adhesions compared to lacZ vector. Levels of tPA in nonmodified (p = 0.021) and modified adhesions (p = 0.001) were elevated while PAI-1 (p = 0.013 and p = 0.001, respectively) and TGF-β1 levels (p = 0.002 and p = 0.016, respectively) were reduced compared with lacZ group. All vectors were not expressed in recurrent adhesions and severity score were not different among groups. EZH2 levels were elevated in de novo nontreated (p = 0.001) and was further increased in recurrent (p = 0.001) nontreated adhesions compared with noninjured peritoneum. Conclusion: Modified adenovirus successfully targeted de novo adhesions but not liver tissues and reduced the severity of de novo adhesions. EZH2 is involved in the development and progression of peritoneal adhesions.

AB - Aim of the study: Adenovector encoding tissue plasminogen activator (tPA) was shown to reduce experimental peritoneal adhesion. We investigated the targeting potential of our modified adenovector, its ability to reduce adhesions and the epigenetic role of histone methyltransferase EZH2 in adhesion formation. Materials and methods: Control lacZ, nonmodified tPA or modified tPA vectors were instilled in the peritoneal cavity after injury in de novo adhesions or after lysis of adhesions in recurrent adhesions. Adhesion severity was scored and adhesions and liver tissues were examined for adenovirus E4 gene and tPA mRNA expression. Levels of tPA, plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-β1 (TGF-β1), and EZH2 expression were measured. Results: E4 transcripts were detected in adhesions of nonmodified and modified and in livers of nonmodified but not in livers of modified de novo adhesions. Both nonmodified (p = 0.021) and modified vectors (p = 0.036) reduced the severity of de novo adhesions compared to lacZ vector. Levels of tPA in nonmodified (p = 0.021) and modified adhesions (p = 0.001) were elevated while PAI-1 (p = 0.013 and p = 0.001, respectively) and TGF-β1 levels (p = 0.002 and p = 0.016, respectively) were reduced compared with lacZ group. All vectors were not expressed in recurrent adhesions and severity score were not different among groups. EZH2 levels were elevated in de novo nontreated (p = 0.001) and was further increased in recurrent (p = 0.001) nontreated adhesions compared with noninjured peritoneum. Conclusion: Modified adenovirus successfully targeted de novo adhesions but not liver tissues and reduced the severity of de novo adhesions. EZH2 is involved in the development and progression of peritoneal adhesions.

KW - gene therapy

KW - histone methyltransferase

KW - peritoneal adhesions

KW - plasminogen activator inhibitor-1

KW - tissue plasminogen activator

KW - transforming growth factor beta-1

UR - http://www.scopus.com/inward/record.url?scp=84989907893&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84989907893&partnerID=8YFLogxK

U2 - 10.1080/08941939.2016.1229366

DO - 10.1080/08941939.2016.1229366

M3 - Article

C2 - 27690696

AN - SCOPUS:84989907893

VL - 30

SP - 78

EP - 87

JO - Journal of Investigative Surgery

JF - Journal of Investigative Surgery

SN - 0894-1939

IS - 2

ER -