Genomewide expression profiles of rat model renal isografts from brain dead donors.
BACKGROUND
It has been well documented that two factors, brain death (BD) and ischemia/reperfusion (I/R) injury, have distinct but overlapping adverse influences on the clinical outcome of renal transplantation.


METHODS
We previously established a rat model of renal isografting from brain dead donors. In the present study, we performed genomic expression profiling with a high-density oligonucleotide microarray to identify genes that were upregulated or downregulated by BD and/or I/R injury.


RESULTS
Among a total of 20,550 genes, most of those upregulated by BD were genes for adhesion molecules and cytokines or for chemokines such as Gro1 and IP-10. When overexpression of these genes was assessed by real-time reverse transcriptase-polymerase chain reaction, it was only observed one hr after the engraftment of kidneys from BD donors and returned to baseline thereafter, indicating the presence of an acute systemic inflammatory response to BD. Analysis of biologic networks demonstrated the activation of specific pathways that were clearly different for BD and I/R injury. The p53 and NFkappaB pathway was involved in the acute response to BD, whereas the Myc, Jun, and c-fos pathway was involved in I/R injury. Investigation of secretory protein genes identified LCN2 and SPP1 as candidate genes for biologic markers.


CONCLUSIONS
Because our experimental system is a good model of renal transplantation from brain dead or living human donors, our data may be useful for elucidating the pathologic processes involved and for identification of novel markers for graft dysfunction of renal transplantation.
Kusaka
Mamoru
M
Department of Urology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. mkusaka@fujita-hu.ac.jp
Kuroyanagi
Yoko
Y
Kowa
Hiroe
H
Nagaoka
Kayuri
K
Mori
Terumi
T
Yamada
Kouji
K
Shiroki
Ryoichi
R
Kurahashi
Hiroki
H
Hoshinaga
Kiyotaka
K
D000818:Animals; D001926:Brain Death / Q000503:physiopathology; D002545:Brain Ischemia / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011917:Rats, Inbred Lew; D015424:Reperfusion; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014019:Tissue Donors; D014185:Transplantation, Isogeneic / Q000502:physiology*