Reperfusion-induced gene expression profiles in rat lung transplantation

Masaomi Yamane, Mingyao Liu, Hiroyuki Kaneda, Stefan Uhlig, Thomas K. Waddell, Shaf Keshavjee

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Ischemia-Reperfusion (I/R) injury after lung transplantation (LTx) can lead to significant morbidity and mortality in recipients. In an attempt to improve our understanding of molecular mechanisms of I/R injury, we examined the changes in gene expression levels in a rat lung transplant model using oligonucleotide microarrays. Lewis rat lung grafts were stored for 6 or 24 h followed by transplantation and reperfusion for 2 h. Lung tissues were taken before and after flushing the grafts, before implantation, and after 2 h of reperfusion. RNA samples were examined with AffymetrixR rat microarray chips and RT-PCR was performed to validate significant changes in gene expression. Microarray analysis showed 404 genes that were upregulated more than 2-fold after reperfusion compared to cold ischemic lungs, and 187 genes that were down-regulated. Using RT-PCR, we confirmed the response pattern of several specific gene transcripts from the microarray analysis. Among these, up-regulation in transcripts of transcription factors, adhesion molecules, pro-coagulant factors and pro-inflammatory cytokines were identified. The differential gene regulation during the I/R process can be considered as molecular signatures for the changes of cellular metabolism, functions and injury. Reperfusion-induced genes related to inflammatory response may contribute to graft dysfunction in LTx.

Original languageEnglish
Pages (from-to)2160-2169
Number of pages10
JournalAmerican Journal of Transplantation
Volume5
Issue number9
DOIs
Publication statusPublished - Sep 1 2005
Externally publishedYes

Keywords

  • Acute lung injury
  • Bioinformatics
  • Ischemia-reperfusion
  • Lung preservation
  • Microarray

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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