Reperfusion-induced gene expression profiles in rat lung transplantation.
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 Affymetrix rat microarray chips and RT-PCR was performed to validate significant changes in gene expression. Microarray analysis showed 404 genes that were up-regulated 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.
Yamane
Masaomi
M
Thoracic Surgery Research Laboratory, Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Liu
Mingyao
M
Kaneda
Hiroyuki
H
Uhlig
Stefan
S
Waddell
Thomas K
TK
Keshavjee
Shaf
S
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D015536:Down-Regulation; D005786:Gene Expression Regulation; D006085:Graft Survival; D007249:Inflammation; D007511:Ischemia; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D016040:Lung Transplantation; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D009926:Organ Preservation; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic; D015854:Up-Regulation
D016207:Cytokines; D010100:Oxygen