Genomewide expression profiles of rat model renal isografts from brain dead donors

Mamoru Kusaka, Yoko Kuroyanagi, Hiroe Kowa, Kayuri Nagaoka, Terumi Mori, Koji Yamada, Ryoichi Shiroki, Hiroki Kurahashi, Kiyotaka Hoshinaga

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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. METHOD. 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 NFκB 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. CONCLUSION. 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.

Original languageEnglish
Pages (from-to)62-70
Number of pages9
JournalTransplantation
Volume83
Issue number1
DOIs
Publication statusPublished - 01-01-2007

Fingerprint

Isografts
Brain Death
Tissue Donors
Kidney
Reperfusion Injury
Brain Ischemia
Kidney Transplantation
Genes
Isogeneic Transplantation
Living Donors
Pathologic Processes
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
Chemokines
Real-Time Polymerase Chain Reaction
Down-Regulation
Biomarkers
Cytokines
Transplants

All Science Journal Classification (ASJC) codes

  • Transplantation

Cite this

Kusaka, Mamoru ; Kuroyanagi, Yoko ; Kowa, Hiroe ; Nagaoka, Kayuri ; Mori, Terumi ; Yamada, Koji ; Shiroki, Ryoichi ; Kurahashi, Hiroki ; Hoshinaga, Kiyotaka. / Genomewide expression profiles of rat model renal isografts from brain dead donors. In: Transplantation. 2007 ; Vol. 83, No. 1. pp. 62-70.
@article{b30db7d37a254d609f403290805b4e2b,
title = "Genomewide expression profiles of rat model renal isografts from brain dead donors",
abstract = "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. METHOD. 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 NFκB 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. CONCLUSION. 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.",
author = "Mamoru Kusaka and Yoko Kuroyanagi and Hiroe Kowa and Kayuri Nagaoka and Terumi Mori and Koji Yamada and Ryoichi Shiroki and Hiroki Kurahashi and Kiyotaka Hoshinaga",
year = "2007",
month = "1",
day = "1",
doi = "10.1097/01.tp.0000250485.53865.b8",
language = "English",
volume = "83",
pages = "62--70",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

Kusaka, M, Kuroyanagi, Y, Kowa, H, Nagaoka, K, Mori, T, Yamada, K, Shiroki, R, Kurahashi, H & Hoshinaga, K 2007, 'Genomewide expression profiles of rat model renal isografts from brain dead donors', Transplantation, vol. 83, no. 1, pp. 62-70. https://doi.org/10.1097/01.tp.0000250485.53865.b8

Genomewide expression profiles of rat model renal isografts from brain dead donors. / Kusaka, Mamoru; Kuroyanagi, Yoko; Kowa, Hiroe; Nagaoka, Kayuri; Mori, Terumi; Yamada, Koji; Shiroki, Ryoichi; Kurahashi, Hiroki; Hoshinaga, Kiyotaka.

In: Transplantation, Vol. 83, No. 1, 01.01.2007, p. 62-70.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genomewide expression profiles of rat model renal isografts from brain dead donors

AU - Kusaka, Mamoru

AU - Kuroyanagi, Yoko

AU - Kowa, Hiroe

AU - Nagaoka, Kayuri

AU - Mori, Terumi

AU - Yamada, Koji

AU - Shiroki, Ryoichi

AU - Kurahashi, Hiroki

AU - Hoshinaga, Kiyotaka

PY - 2007/1/1

Y1 - 2007/1/1

N2 - 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. METHOD. 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 NFκB 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. CONCLUSION. 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.

AB - 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. METHOD. 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 NFκB 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. CONCLUSION. 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.

UR - http://www.scopus.com/inward/record.url?scp=33846259761&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846259761&partnerID=8YFLogxK

U2 - 10.1097/01.tp.0000250485.53865.b8

DO - 10.1097/01.tp.0000250485.53865.b8

M3 - Article

C2 - 17220792

AN - SCOPUS:33846259761

VL - 83

SP - 62

EP - 70

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 1

ER -