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The potential of antisense oligonucleotide inhibiting chronic rejection of renal allografts

Research Project

Project/Area Number 15390498
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionFUJITA HEALTH UNIVERSITY

Principal Investigator

HOSHINAGA Kiyotaka  FUJITA HEALTH UNIVERSITY, School of Medicine, Professor, 医学部, 教授 (30229174)

Co-Investigator(Kenkyū-buntansha) SHIROKI Ryoichi  FUJITA HEALTH UNIVERSITY, School of Medicine, Associate Professor, 医学部, 助教授 (70226330)
KUSAKA Mamoru  FUJITA HEALTH UNIVERSITY, School of Medicine, Assistant Professor, 医学部, 講師 (40309141)
佐々木 ひと美  藤田保健衛生大学, 医学部, 講師 (00319261)
桑原 勝孝  藤田保健衛生大学, 医学部, 助手 (40322549)
樋口 徹  藤田保健衛生大学, 医学部, 助手 (60308905)
Project Period (FY) 2003 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥16,600,000 (Direct Cost: ¥16,600,000)
Fiscal Year 2006: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2004: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥7,400,000 (Direct Cost: ¥7,400,000)
Keywordsbrain death / ischemia / reperfusion injury / real time PCR / microarray / chronic rejection
Research Abstract

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. We previously established a rat model of renal isografting from brain dead donors. We performed genomic expression profiling with a microarray to identify genes that were upregulated or downregulated by BD and/or I/R injury. Most of those upregulated by BD were genes for adhesion molecules and cytokines, or for chemokines such as Grol and IP-10. Analysis of biological 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 biological markers. In clinical study, we performed gene expression profiling using one-hour … More biopsy samples from DCD kidneys and compared with those from living sources. All graft biopsies were performed 1 hour after reperfusion (DCD n=8,LD n=15). The expression profile of 20,173 genes was analyzed. 178 genes were up-regulated and 120 genes down-regulated in DCD kidneys. Expression of Osteopontin, chemokines, adhesion molecule and heat shock proteins was up-regulated in the kidneys from DCD. This is the first demonstration of an analysis of global gene expression using one-hour biopsy samples from DCD kidneys. These results provide new insight into the identification of novel target genes for the development of therapeutics and for determining graft viability of kidneys from DCD. The final study evaluated serum NGAL as a potential specific parameter to predict early functional recovery of transplanted DCD kidneys. In patients undergoing a living-related KTx from a living donor (n=11), serum NGAL level decreased rapidly after KTx, and only in two cases, with serum NGAL levels over 400 ng/ml on post operative day 1 (POD1), as HD required due to DGF. In contrast, all patients undergoing a KTx from a DCD (n=5) required HD due to DGF. Even in these cases, serum NGAL levels decreased rapidly several days after a KTx prior to the recovery of urine output and preceding the decrease in serum creatinine level. The pattern of decline in serum NGAL was biphasic, the decrease after the second peak indicating a functional recovery within the next several days. These data suggest that monitoring of serum NGAL levels may allow us to predict graft recovery and the need for HD after a KTx from a DCD. Less

Report

(5 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (17 results)

All 2007 2006 2005 Other

All Journal Article (16 results) Publications (1 results)

  • [Journal Article] Genomewide expression profiles of rat model renal isografts from brain dead donors.2007

    • Author(s)
      M.Kusaka, Y, Kuroyanagi, H, Kowa, et al.
    • Journal Title

      Transplantation Vol 83

      Pages: 62-70

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Serum neutrophil gelatinase-associated lipocalin as a predictor of organ recovery from delayed graft function after kidney transplantation from donors after cardiac death2007

    • Author(s)
      M.Kusaka, Y, Kuroyanagi, T, Mori, et al.
    • Journal Title

      Cell Transplantation (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Genomewide expression profiles of rat model renal isografts from brain dead donors.2007

    • Author(s)
      M.Kusaka, Y, Kuroyanagi, H, Kowa, et al.
    • Journal Title

      Transplantation (83)

      Pages: 62-70

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Genomewide expression profiles of rat model renal isografts from brain dead donors.2007

    • Author(s)
      M.Kusaka, Y.Kuroyanagi, H.Kowa, et al.
    • Journal Title

      Transplantation Vol.83

      Pages: 62-70

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Up-regulation of osteopontin, chemokines, adhesion molecule, and heat shock proteins in 1-hour biopsy from cardiac death donor kidneys2006

    • Author(s)
      M.Kusaka, Y, Kuroyanagi, T, Mori, et al.
    • Journal Title

      Transplant Proc Vol 38

      Pages: 3347-3350

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Up-regulation of osteopontin, chemokines, adhesion molecule, and heat shock proteins in 1-hour biopsy from cardiac death donor kidneys2006

    • Author(s)
      M.Kusaka, Y, Kuroyanagi, T, Mori, et al.
    • Journal Title

      Transplant Proc (38)

      Pages: 3347-3350

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Up-regulation of osteopontin, chemokines, adhesion molecule, and heat shock proteins in 1-hour biopsy from cardiac death donor kidneys2006

    • Author(s)
      M.Kusaka, Y.Kuroyanagi, T.Mori, et al.
    • Journal Title

      Transplant Proc Vol.38

      Pages: 3347-3350

    • Related Report
      2006 Annual Research Report
  • [Journal Article] IP-10, Apoptotic Genes, and Calcineurin Subtype mRNA Kinetics Occurring in Rat Renal Isografts from Brain Death Domors2005

    • Author(s)
      M.Kusaka, N.Fukami, H.Sasaki, et al.
    • Journal Title

      Transplantation Proc Vol 37

      Pages: 361-363

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Gene Expression Profile in Rat Renal Isografts from Brain Death Donors2005

    • Author(s)
      M.Kusaka, K.Yamada, Y.Kuroyanagi, et al.
    • Journal Title

      Transplantation Proc Vol 37

      Pages: 364-366

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] IP-10,Apoptotic Genes, and Calcineurin Subtype mRNA Kinetics Occurring in Rat Renal Isografts from Brain Death Domors2005

    • Author(s)
      M.Kusaka, N.Fukami, H.Sasaki, et al.
    • Journal Title

      Transplant Proc (37)

      Pages: 361-363

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Gene Expression Profile in Rat Renal Isografts from Brain Death Donors2005

    • Author(s)
      M.Kusaka, K.Yamada, Y.Kuroyanagi, et al.
    • Journal Title

      Transplant Proc (37)

      Pages: 364-366

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Gene Expression Profile in Rat Renal Isografts from Brain Death Donors2005

    • Author(s)
      M.Kusaka, K.Yamada, Y.Kuroyanagi, et al.
    • Journal Title

      Transplantation Proceedings Vol 37

      Pages: 364-366

    • Related Report
      2005 Annual Research Report
  • [Journal Article] IP-10, Apoptotic Genes, and Calcineurin Subtype mRNA Kinetics Occurring in Rat Renal Isografts from Brain Death Domors2005

    • Author(s)
      M.Kusaka, N.Fukami, H.Sasaki, et al.
    • Journal Title

      Transplantation Proceedings Vol 37

      Pages: 361-363

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Gene Expression Profile in Rat Renal Isografts from Brain Death Donors2005

    • Author(s)
      M.Kusaka, K.Yamada, Y.Kuroyanagi, et al.
    • Journal Title

      Transplantation Proceedings Vol 37/1

      Pages: 364-366

    • Related Report
      2004 Annual Research Report
  • [Journal Article] IP-10, Apoptotic Genes, and Calcineurin Subtype mRNA Kinetics Occurring in Rat Renal Isografts from Brain Death Domors2005

    • Author(s)
      M.Kusaka, N.Fukami, H.Sasaki, et al.
    • Journal Title

      Transplantation Proceedings Vol 37/1

      Pages: 361-363

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Serum neutrophil gel atinase-associated lipocalin as a predictor of organ recovery from delayed graft function after kidney transplantation from donors after cardiac death

    • Author(s)
      M.Kusaka, Y, Kuroyanagi, T, Mori, et al.
    • Journal Title

      Cell Transplantation (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Publications] 日下 守, 星長清隆: "当院における心停止ドナーからの献腎移植の実際と虚血再灌流障害に対する戦略"低温医学. 29-2. 32-37 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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