Effect of ischemic preconditioning on the genomic response to reperfusion injury in deceased donor liver transplantation.
Ischemic preconditioning (IP) is an effective method for protecting organs from ischemia/reperfusion (IR) injury; however, the molecular basis of this protective effect is poorly understood. This study assessed the gene expression profile in liver allografts during transplantation and evaluated the...
Main Authors: | , , , , , , , |
---|---|
Format: | Journal article |
Language: | English |
Published: |
2009
|
_version_ | 1797097027981541376 |
---|---|
author | Jassem, W Fuggle, S Thompson, R Arno, M Taylor, J Byrne, J Heaton, N Rela, M |
author_facet | Jassem, W Fuggle, S Thompson, R Arno, M Taylor, J Byrne, J Heaton, N Rela, M |
author_sort | Jassem, W |
collection | OXFORD |
description | Ischemic preconditioning (IP) is an effective method for protecting organs from ischemia/reperfusion (IR) injury; however, the molecular basis of this protective effect is poorly understood. This study assessed the gene expression profile in liver allografts during transplantation and evaluated the impact of IP. Prereperfusion and postreperfusion biopsy specimens from livers subjected to IP (n = 19) or no preconditioning (the IR group; n = 16) were obtained. Total RNA was extracted and hybridized to GeneChip microarrays, and the findings were validated with real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). IP livers showed less of an increase in aspartate aminotransferase after transplantation. A microarray analysis of the IR group showed increased expression of 57 genes mainly involved in cell death, inflammation and immune response, stress, and modulation of the cell cycle. The IP group showed attenuation of the expression of these genes after reperfusion. Additionally, IP led to increased expression of 43 genes involved in growth and maintenance, cell-cycle regulation, proliferation, and development. The expression of the 12 most significant genes was validated in all patients with real-time qRT-PCR, and the fold changes of a number of genes correlated with clinical parameters and graft outcomes. IP protection of liver allografts was associated with a reduction in the expression of immune response genes and promotion of those involved in protection and repair. |
first_indexed | 2024-03-07T04:49:50Z |
format | Journal article |
id | oxford-uuid:d490b012-419b-4d50-a2f2-80619d1c9c2a |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T04:49:50Z |
publishDate | 2009 |
record_format | dspace |
spelling | oxford-uuid:d490b012-419b-4d50-a2f2-80619d1c9c2a2022-03-27T08:19:31ZEffect of ischemic preconditioning on the genomic response to reperfusion injury in deceased donor liver transplantation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d490b012-419b-4d50-a2f2-80619d1c9c2aEnglishSymplectic Elements at Oxford2009Jassem, WFuggle, SThompson, RArno, MTaylor, JByrne, JHeaton, NRela, MIschemic preconditioning (IP) is an effective method for protecting organs from ischemia/reperfusion (IR) injury; however, the molecular basis of this protective effect is poorly understood. This study assessed the gene expression profile in liver allografts during transplantation and evaluated the impact of IP. Prereperfusion and postreperfusion biopsy specimens from livers subjected to IP (n = 19) or no preconditioning (the IR group; n = 16) were obtained. Total RNA was extracted and hybridized to GeneChip microarrays, and the findings were validated with real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). IP livers showed less of an increase in aspartate aminotransferase after transplantation. A microarray analysis of the IR group showed increased expression of 57 genes mainly involved in cell death, inflammation and immune response, stress, and modulation of the cell cycle. The IP group showed attenuation of the expression of these genes after reperfusion. Additionally, IP led to increased expression of 43 genes involved in growth and maintenance, cell-cycle regulation, proliferation, and development. The expression of the 12 most significant genes was validated in all patients with real-time qRT-PCR, and the fold changes of a number of genes correlated with clinical parameters and graft outcomes. IP protection of liver allografts was associated with a reduction in the expression of immune response genes and promotion of those involved in protection and repair. |
spellingShingle | Jassem, W Fuggle, S Thompson, R Arno, M Taylor, J Byrne, J Heaton, N Rela, M Effect of ischemic preconditioning on the genomic response to reperfusion injury in deceased donor liver transplantation. |
title | Effect of ischemic preconditioning on the genomic response to reperfusion injury in deceased donor liver transplantation. |
title_full | Effect of ischemic preconditioning on the genomic response to reperfusion injury in deceased donor liver transplantation. |
title_fullStr | Effect of ischemic preconditioning on the genomic response to reperfusion injury in deceased donor liver transplantation. |
title_full_unstemmed | Effect of ischemic preconditioning on the genomic response to reperfusion injury in deceased donor liver transplantation. |
title_short | Effect of ischemic preconditioning on the genomic response to reperfusion injury in deceased donor liver transplantation. |
title_sort | effect of ischemic preconditioning on the genomic response to reperfusion injury in deceased donor liver transplantation |
work_keys_str_mv | AT jassemw effectofischemicpreconditioningonthegenomicresponsetoreperfusioninjuryindeceaseddonorlivertransplantation AT fuggles effectofischemicpreconditioningonthegenomicresponsetoreperfusioninjuryindeceaseddonorlivertransplantation AT thompsonr effectofischemicpreconditioningonthegenomicresponsetoreperfusioninjuryindeceaseddonorlivertransplantation AT arnom effectofischemicpreconditioningonthegenomicresponsetoreperfusioninjuryindeceaseddonorlivertransplantation AT taylorj effectofischemicpreconditioningonthegenomicresponsetoreperfusioninjuryindeceaseddonorlivertransplantation AT byrnej effectofischemicpreconditioningonthegenomicresponsetoreperfusioninjuryindeceaseddonorlivertransplantation AT heatonn effectofischemicpreconditioningonthegenomicresponsetoreperfusioninjuryindeceaseddonorlivertransplantation AT relam effectofischemicpreconditioningonthegenomicresponsetoreperfusioninjuryindeceaseddonorlivertransplantation |