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Conference Paper: The knockout of telomere-independent Rap1 attenuates hepatic ischemia reperfusion injury by suppressing neutrophil activation

TitleThe knockout of telomere-independent Rap1 attenuates hepatic ischemia reperfusion injury by suppressing neutrophil activation
Authors
KeywordsMedical sciences
Gastroenterology medical sciences
Surgery
Issue Date2014
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jtoc/106570021
Citation
The 2014 Joint International Congress of ILTS, ELITA and LICAGE, London, UK., 4-7 June 2014. In Liver Transplantation, 2014, v. 20 suppl. S1, p. S236, abstract P-272 How to Cite?
AbstractBACKGROUND AND AIM: Telomere-independent Rap1, a component of the telosome protein complex, is a critical regulator of NF-κB and mediates inflammatory responses. However, the role of Rap1 on liver injury has not been clearly explored. In this study, we aim to investigate the roles of Rap1 in hepatic ischemia reperfusion injury (IRI) and to explore the underlying molecular mechanism. METHODS: The intragraft Rap1 expression profile, inflammatory cytokines/chemokines, and neutrophil infiltration were examined in human liver graft biopsies. The role of Rap1 in liver injury was also explored in Rap1 knockout mice with hepatic IRI. Histological changes, liver function, expressions of neutrophil chemoattractants and adhesion factors, together with neutrophil infiltration were compared between Rap1 knockout mice and wild type controls. The interaction between hepatic endothelial cells and neutrophil migration/activation was further explored under the regulation of RAP1. In addition, primary neutrophils isolated from Rap1 knockout or wild type mice were activated by fMLP. The migration and activation of neutrophil were compared between those primary neutrophils from Rap1 knockout mice and wild type controls. RESULTS: Over-expression of intragraft Rap1 was associated with lots of neutrophil infiltration (36.2/HPF in liver graft vs 3.5/HPF in normal liver, P=0.00) and high expressions of inflammatory cytokines/chemokines in human liver graft after transplantation. High expression of Rap1 was mainly expressed in neutrophils in liver graft. In mouse model, sinusoidal damage, liver function (ALT: 395.59 vs 280.67 U/L, p=0.024; AST: 522.886 vs 368.628 U/L, p=0.025), neutrophil infiltration (19.7 vs 9.2/HPF, p=0.001), expressions of neutrophil chemoattractants (CXCL2: 30.9 vs 12.7, p=0.037) and adhesion factors (ICAM1: 4.2 vs 2.4, p=0.049; VCAM1:4.5 vs 2.1 folds of normal liver; p=0.026), and activation of NF-κB were attenuated in Rap1 knockout mice. Furthermore, the knockout of Rap1 decreased the expressions of neutrophil chemoattractants and adhesion factors in endothelial cells and further suppressed neutrophil migration and activation. CONCLUSION: The knockout of Rap1 attenuates hepatic IRI by suppressing the neutrophil migration and activation. Rap1 might be the potential treatment target for prevention of liver graft injury.
DescriptionPoster Session 2: P-272
This journal suppl. entitled: The ILTS 20th Annual International Congress
Persistent Identifierhttp://hdl.handle.net/10722/204491
ISSN
2015 Impact Factor: 3.951
2015 SCImago Journal Rankings: 1.763

 

DC FieldValueLanguage
dc.contributor.authorMan, K-
dc.contributor.authorLi, C-
dc.contributor.authorNg, KTP-
dc.contributor.authorLo, CM-
dc.date.accessioned2014-09-19T23:57:03Z-
dc.date.available2014-09-19T23:57:03Z-
dc.date.issued2014-
dc.identifier.citationThe 2014 Joint International Congress of ILTS, ELITA and LICAGE, London, UK., 4-7 June 2014. In Liver Transplantation, 2014, v. 20 suppl. S1, p. S236, abstract P-272-
dc.identifier.issn1527-6465-
dc.identifier.urihttp://hdl.handle.net/10722/204491-
dc.descriptionPoster Session 2: P-272-
dc.descriptionThis journal suppl. entitled: The ILTS 20th Annual International Congress-
dc.description.abstractBACKGROUND AND AIM: Telomere-independent Rap1, a component of the telosome protein complex, is a critical regulator of NF-κB and mediates inflammatory responses. However, the role of Rap1 on liver injury has not been clearly explored. In this study, we aim to investigate the roles of Rap1 in hepatic ischemia reperfusion injury (IRI) and to explore the underlying molecular mechanism. METHODS: The intragraft Rap1 expression profile, inflammatory cytokines/chemokines, and neutrophil infiltration were examined in human liver graft biopsies. The role of Rap1 in liver injury was also explored in Rap1 knockout mice with hepatic IRI. Histological changes, liver function, expressions of neutrophil chemoattractants and adhesion factors, together with neutrophil infiltration were compared between Rap1 knockout mice and wild type controls. The interaction between hepatic endothelial cells and neutrophil migration/activation was further explored under the regulation of RAP1. In addition, primary neutrophils isolated from Rap1 knockout or wild type mice were activated by fMLP. The migration and activation of neutrophil were compared between those primary neutrophils from Rap1 knockout mice and wild type controls. RESULTS: Over-expression of intragraft Rap1 was associated with lots of neutrophil infiltration (36.2/HPF in liver graft vs 3.5/HPF in normal liver, P=0.00) and high expressions of inflammatory cytokines/chemokines in human liver graft after transplantation. High expression of Rap1 was mainly expressed in neutrophils in liver graft. In mouse model, sinusoidal damage, liver function (ALT: 395.59 vs 280.67 U/L, p=0.024; AST: 522.886 vs 368.628 U/L, p=0.025), neutrophil infiltration (19.7 vs 9.2/HPF, p=0.001), expressions of neutrophil chemoattractants (CXCL2: 30.9 vs 12.7, p=0.037) and adhesion factors (ICAM1: 4.2 vs 2.4, p=0.049; VCAM1:4.5 vs 2.1 folds of normal liver; p=0.026), and activation of NF-κB were attenuated in Rap1 knockout mice. Furthermore, the knockout of Rap1 decreased the expressions of neutrophil chemoattractants and adhesion factors in endothelial cells and further suppressed neutrophil migration and activation. CONCLUSION: The knockout of Rap1 attenuates hepatic IRI by suppressing the neutrophil migration and activation. Rap1 might be the potential treatment target for prevention of liver graft injury.-
dc.languageeng-
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jtoc/106570021-
dc.relation.ispartofLiver Transplantation-
dc.rightsLiver Transplantation. Copyright © John Wiley & Sons, Inc.-
dc.subjectMedical sciences-
dc.subjectGastroenterology medical sciences-
dc.subjectSurgery-
dc.titleThe knockout of telomere-independent Rap1 attenuates hepatic ischemia reperfusion injury by suppressing neutrophil activation-
dc.typeConference_Paper-
dc.identifier.emailMan, K: kwanman@hku.hk-
dc.identifier.emailNg, KTP: ledodes@hku.hk-
dc.identifier.emailLo, CM: chungmlo@hkucc.hku.hk-
dc.identifier.authorityMan, K=rp00417-
dc.identifier.authorityNg, KTP=rp01720-
dc.identifier.authorityLo, CM=rp00412-
dc.identifier.doi10.1002/lt.23901-
dc.identifier.hkuros237559-
dc.identifier.volume20-
dc.identifier.issuesuppl. S1-
dc.identifier.spageS236, abstract P-272-
dc.identifier.epageS236, abstract P-272-
dc.publisher.placeUnited States-

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