Regulation of molecular pathways in ischemia-reperfusion injury after liver transplantation

Ricardo C. Gehrau, Valeria Mas, Catherine I. Dumur, Danielle E. Ladie, Jihee L. Suh, Samuel Luebbert, Daniel Maluf

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background. Ischemia-reperfusion (I/R) injury is a multifactorial phenomenon that occurs during the transplant event and frequently compromises early graft function after liver transplantation (LT). Current comprehension of molecular mechanisms and regulation processes of I/R injury lacks clarity. MicroRNA (miRNA) regulation results critical in several biological processes. Methods. This study evaluated gene expression and miRNA expression profiles using microarrays in 34 graft biopsies collected at preimplantation (L1) and at 90 min postreperfusion (L2) from consecutives deceased-donor LTrecipients. miRNA profiles were first analyzed. Data integration analysis (gene expression/miRNA expression) aimed to identify potential target genes for each identified miRNA from the L1/L2 differential gene expression profile. Results. Pairwise comparison analyses identified 40 miRNAs and 3168 significantly differentially expressed genes at postreperfusion time compared with preimplantation time. Pathway analysis of miRNAs associated these profiles with antiapoptosis, inhibition of cellular proliferation, and proinflammatory processes. Target analysis identified an miRNA-associated molecular profile of 2172 genes involved in cellular growth and proliferation modulation by cell cycle regulation, cell death and survival, and proinflammatory and anti-inflammatory processes. miRNAindependent genes involved proinflammatory molecules. Conclusion. We identified a miRNA profile involved in posttranscriptional regulatory mechanisms in I/R injury post- LT. A better understanding of these molecular processes involved in I/R may contribute to develop new strategies to minimize graft injury.

Original languageEnglish (US)
Pages (from-to)926-934
Number of pages9
JournalTransplantation
Volume96
Issue number10
DOIs
StatePublished - Aug 29 2013

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Reperfusion Injury
MicroRNAs
Liver Transplantation
Transplants
Genes
Cell Proliferation
Biological Phenomena
Gene Expression
Transcriptome
Reperfusion
Cell Survival
Cell Cycle
Cell Death
Anti-Inflammatory Agents
Ischemia
Biopsy
Wounds and Injuries
Growth

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Regulation of molecular pathways in ischemia-reperfusion injury after liver transplantation. / Gehrau, Ricardo C.; Mas, Valeria; Dumur, Catherine I.; Ladie, Danielle E.; Suh, Jihee L.; Luebbert, Samuel; Maluf, Daniel.

In: Transplantation, Vol. 96, No. 10, 29.08.2013, p. 926-934.

Research output: Contribution to journalArticle

Gehrau, Ricardo C. ; Mas, Valeria ; Dumur, Catherine I. ; Ladie, Danielle E. ; Suh, Jihee L. ; Luebbert, Samuel ; Maluf, Daniel. / Regulation of molecular pathways in ischemia-reperfusion injury after liver transplantation. In: Transplantation. 2013 ; Vol. 96, No. 10. pp. 926-934.
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abstract = "Background. Ischemia-reperfusion (I/R) injury is a multifactorial phenomenon that occurs during the transplant event and frequently compromises early graft function after liver transplantation (LT). Current comprehension of molecular mechanisms and regulation processes of I/R injury lacks clarity. MicroRNA (miRNA) regulation results critical in several biological processes. Methods. This study evaluated gene expression and miRNA expression profiles using microarrays in 34 graft biopsies collected at preimplantation (L1) and at 90 min postreperfusion (L2) from consecutives deceased-donor LTrecipients. miRNA profiles were first analyzed. Data integration analysis (gene expression/miRNA expression) aimed to identify potential target genes for each identified miRNA from the L1/L2 differential gene expression profile. Results. Pairwise comparison analyses identified 40 miRNAs and 3168 significantly differentially expressed genes at postreperfusion time compared with preimplantation time. Pathway analysis of miRNAs associated these profiles with antiapoptosis, inhibition of cellular proliferation, and proinflammatory processes. Target analysis identified an miRNA-associated molecular profile of 2172 genes involved in cellular growth and proliferation modulation by cell cycle regulation, cell death and survival, and proinflammatory and anti-inflammatory processes. miRNAindependent genes involved proinflammatory molecules. Conclusion. We identified a miRNA profile involved in posttranscriptional regulatory mechanisms in I/R injury post- LT. A better understanding of these molecular processes involved in I/R may contribute to develop new strategies to minimize graft injury.",
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