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Article: Non-viral Smad7 gene delivery and attenuation of postoperative peritoneal adhesion in an experimental model

TitleNon-viral Smad7 gene delivery and attenuation of postoperative peritoneal adhesion in an experimental model
Authors
Issue Date2009
PublisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.bjs.co.uk
Citation
British Journal Of Surgery, 2009, v. 96 n. 11, p. 1323-1335 How to Cite?
AbstractBackground: Postoperative intra-abdominal adhesion is associated with high morbidity and mortality. Smad7, a protein that occupies a strategic position in fibrogenesis, inhibits the transforming growth factor (TGF) β/Smad signalling pathway. In this study the therapeutic potential of exogenous Smad7 in preventing fibrogenesis in postoperative intra-abdominal adhesion was investigated. Methods: Intra-abdominal adhesion was induced in a rodent model by peritoneal abrasion. Smad7 was delivered into the peritoneal cavity by a non-viral ultrasound-microbubble-mediated naked gene transfection system. The effect of Smad7 transgene on adhesion formation was studied by measuring changes in TGF-β, fibrogenic factors, α-SMA and Smad2/3 activation in the anterior abdominal wall. Results: Four weeks after surgical abrasion, all rats developed significant peritoneal adhesion with enhanced TGF-β expression, increased levels of extracellular matrix components and activated myofibroblasts, accompanied by decreased Smad7 expression and increased Smad2/3 activation. In rats treated with the Smad7 transgene, the incidence and severity of peritoneal adhesion were significantly reduced, with biochemical downregulation of fibrogenic factors and inhibition of Smad2/3 activation. Serial quantitation using magnetic resonance imaging revealed a significant reduction in adhesion areas from day 14 onwards. Conclusion: Ultrasound-microbubble-mediated gene transfection provides timely targeted gene delivery for the treatment of postoperative peritoneal adhesions. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/129229
ISSN
2015 Impact Factor: 5.596
2015 SCImago Journal Rankings: 2.966
ISI Accession Number ID
Funding AgencyGrant Number
Government Matching Grant Scheme (Hong Kong)
L & T Charitable Foundation
House of INDOCAFE
US patent publicationUS-2008-0114287-A1
Funding Information:

The authors dunk Dr M. F. Lam for surgical advice, Professor H. Y Lan Or advice oil gene therapy and Ms A. W. L Tsang for technical assistance H.G. was a Mrs Ivy Wu Fellow at the University of Hong Kong. The study was supported by the Government Matching Grant Scheme (Hong Kong), the L & T Charitable Foundation and the House of INDOCAFE The gene therapy delivery system has been filed under US patent publication no US-2008-0114287-A1. The authors, declare no conflict of Interest.

References

 

DC FieldValueLanguage
dc.contributor.authorGuo, Hen_HK
dc.contributor.authorLeung, JCKen_HK
dc.contributor.authorCheung, JSen_HK
dc.contributor.authorChan, LYYen_HK
dc.contributor.authorWu, EXen_HK
dc.contributor.authorLai, KNen_HK
dc.date.accessioned2010-12-23T08:33:46Z-
dc.date.available2010-12-23T08:33:46Z-
dc.date.issued2009en_HK
dc.identifier.citationBritish Journal Of Surgery, 2009, v. 96 n. 11, p. 1323-1335en_HK
dc.identifier.issn0007-1323en_HK
dc.identifier.urihttp://hdl.handle.net/10722/129229-
dc.description.abstractBackground: Postoperative intra-abdominal adhesion is associated with high morbidity and mortality. Smad7, a protein that occupies a strategic position in fibrogenesis, inhibits the transforming growth factor (TGF) β/Smad signalling pathway. In this study the therapeutic potential of exogenous Smad7 in preventing fibrogenesis in postoperative intra-abdominal adhesion was investigated. Methods: Intra-abdominal adhesion was induced in a rodent model by peritoneal abrasion. Smad7 was delivered into the peritoneal cavity by a non-viral ultrasound-microbubble-mediated naked gene transfection system. The effect of Smad7 transgene on adhesion formation was studied by measuring changes in TGF-β, fibrogenic factors, α-SMA and Smad2/3 activation in the anterior abdominal wall. Results: Four weeks after surgical abrasion, all rats developed significant peritoneal adhesion with enhanced TGF-β expression, increased levels of extracellular matrix components and activated myofibroblasts, accompanied by decreased Smad7 expression and increased Smad2/3 activation. In rats treated with the Smad7 transgene, the incidence and severity of peritoneal adhesion were significantly reduced, with biochemical downregulation of fibrogenic factors and inhibition of Smad2/3 activation. Serial quantitation using magnetic resonance imaging revealed a significant reduction in adhesion areas from day 14 onwards. Conclusion: Ultrasound-microbubble-mediated gene transfection provides timely targeted gene delivery for the treatment of postoperative peritoneal adhesions. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons Ltd.en_HK
dc.languageengen_US
dc.publisherJohn Wiley & Sons Ltd. The Journal's web site is located at http://www.bjs.co.uken_HK
dc.relation.ispartofBritish Journal of Surgeryen_HK
dc.rightsBritish Journal of Surgery. Copyright © John Wiley & Sons Ltd.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsThis is a preprint of an article published in British Journal of Surgery, 2009, v. 96 n. 11, p. 1323-1335-
dc.subject.meshGene Transfer Techniques-
dc.subject.meshGenetic Vectors - physiology-
dc.subject.meshPeritoneal Diseases - metabolism - pathology - prevention and control-
dc.subject.meshSmad7 Protein - administration and dosage - genetics-
dc.subject.meshTissue Adhesions - metabolism - pathology - prevention and control-
dc.titleNon-viral Smad7 gene delivery and attenuation of postoperative peritoneal adhesion in an experimental modelen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0007-1323&volume=96&issue=11&spage=1323&epage=1335&date=2009&atitle=Non-viral+Smad7+gene+delivery+and+attenuation+of+postoperative+peritoneal+adhesion+in+an+experimental+model-
dc.identifier.emailLeung, JCK: jckleung@hku.hken_HK
dc.identifier.emailWu, EX: ewu1@hkucc.hku.hken_HK
dc.identifier.emailLai, KN: knlai@hku.hken_HK
dc.identifier.authorityLeung, JCK=rp00448en_HK
dc.identifier.authorityWu, EX=rp00193en_HK
dc.identifier.authorityLai, KN=rp00324en_HK
dc.description.naturepostprint-
dc.identifier.doi10.1002/bjs.6722en_HK
dc.identifier.pmid19847872-
dc.identifier.scopuseid_2-s2.0-70350497690en_HK
dc.identifier.hkuros177161en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-70350497690&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume96en_HK
dc.identifier.issue11en_HK
dc.identifier.spage1323en_HK
dc.identifier.epage1335en_HK
dc.identifier.isiWOS:000271556900016-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridGuo, H=55468645700en_HK
dc.identifier.scopusauthoridLeung, JCK=7202180349en_HK
dc.identifier.scopusauthoridCheung, JS=16174280400en_HK
dc.identifier.scopusauthoridChan, LYY=55182644100en_HK
dc.identifier.scopusauthoridWu, EX=7202128034en_HK
dc.identifier.scopusauthoridLai, KN=7402135706en_HK
dc.identifier.citeulike6038240-

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