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Celluar mechanism of fibrosis in the obstructed kidney

Research Project

Project/Area Number 09671601
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionTOHOKU University

Principal Investigator

FUKUZAKI Atsushi  Tohoku Univ., Hospital, Lecturer, 医学部・附属病院, 講師 (70133957)

Co-Investigator(Kenkyū-buntansha) KANETO Hiroyuki  Tohoku Univ, Sch of Med, Research Associate, 医学部, 助手 (00224626)
川村 貞文  東北大学, 医学部, 助手 (40292213)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordskidney / fibrosis / obstruction / siqnal transduction / トランスフォーミンググロースファクターβ / アンジオテンシンII / 尿路閉鎖 / 腎線維化
Research Abstract

Renal interstitial fibrosis is a common consequence of long-standing obstructive uropathy. Fibrosis likely develops due to an imbalance between extra cellular matrix synthesis and deposition and matrix degradation. The protease plasmin can degrade avariety of extra cellular matrix molecules. Plasmin generation from plasminogen is highly regulated by the interaction of plasminogen activator inhibitor-1 (PAL-i). It has recently been shown that angiotensin II acts both directly and through induction of TGF-beta to alter the PAI-1/plasmin system. We investigated PAL-i activity in the obstructed kidney and demonstrated increased PAL-i expression in the unilaterally obstructed rat kidney. The result indicates that angiotensin II dependent inhibition of plasmin system by increased PAI-1 activity may play an important role intubulointerstitial fibrosis in the obstructed kidney. In addition, we demonstrated angiotensin II dependent cytokine expression and inflammatory cell infiltration contribute to the tubulointerstitial fibrosis and progression of the disease in the human obstructed kidneys. Furthermore, we clarified persistent activation of renin-angiotensinsystem (RAS) in the patient with chronic ureteral obstruction. These results indicate that inhibition of RAS may have a key role to protect obstructed kidneys from progression of the disease.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] 折笠精一: "萎縮性腎盂腎炎" 日本臨床. 別冊. 229-234 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 折笠精一: "閉塞性腎盂腎炎" 日本臨床. 別冊. 272-274 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 折笠精一: "閉塞性腎症" 日本臨床. 別冊. 688-690 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 福崎 篤: "閉塞性尿路疾患、水腎症" 腎と透析. 47. 印刷中 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shigenori Ikeda: "Role of protein kinase C in cisplatin Nephrotoxicity" International Journal of Urology. 印刷中 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 福崎 篤: "閉塞性腎症による尿細管、間質性腎障害" 日本内科学会雑誌. 88. 印刷中 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 折笠精一: "小児泌尿器科学書" 金原出版, 483 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Orikasa S,Fukuzaki A: "Atrophic pyelonephritis." Nihon Rinsho, Suppl.16. 229-234 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Orikasa S,Fukuzaki A: "Obstructive pyelonephritis" Nihon Rinsho, Suppl.16. 272-274 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Orikasa S,Fukuzaki A: "Obstructive nephropathy." Nihon Rinsho, Suppl.17. 688-690 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Orikasa S,Fukuzaki A: "Renal physiology and function." Text book of Pediatric Urology, Kanehara Shuppan, Tokyo. 117-123 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fukuzaki A: "Hydronephrosis" Jin to Toseki. 47 (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ikeda S,Fukuzaki A,Kaneto H,Ishidoya S,Orikasa S: "Role of protein kinase C in cisplatin nephrotoxicity." Int J Urol. 6 (in press). 245-250 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fukuzaki A: "Tubulointerstitiak fibrosis in obstructive nephropathy" Nihon Naika Gakkai Zasshi. 88 (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 折笠精一: "萎縮性腎盂腎炎" 日本臨床. 別冊. 229-234 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 折笠精一: "閉塞性腎盂腎炎" 日本臨床. 別冊. 272-274 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 折笠精一: "閉塞性腎症" 日本臨床. 別冊. 688-690 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 福崎 篤: "閉塞性尿路疾・水腎症" 腎と透析. 47 印刷中. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shigenori Ikeda: "Role of protein kinase C in cisplatin nephrotoxicity" International Journal of Urology. 発表予定. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 福崎 篤: "閉塞性腎症による尿細管・間質性腎障害" 日本内科学会雑誌. 88 発表予定. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 折笠精一: "小児泌尿器科学書" 金原出版, 483 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kaneko H, Fukuzaki A, et al: "mRNA expressior for chemokines in the rat kidney during unilateral obstruction" J.Am.Soc.Nephrol.7・(9). 1705 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 折笠精一, 福崎篤: "萎縮性腎盂腎炎" 日本臨床. 別冊・(16). 229-234 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 折笠精一, 福崎篤: "閉塞性腎盂腎炎" 日本臨床. 別冊・(16). 272-274 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 折笠精一, 福崎篤: "閉塞性腎症" 日本臨床. 別冊・(17). 688-690 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Fukuzaki,A, et al: "Role of protein kinase C in clsplatin nephro toxicity" Brit.J.Urol.80(suppl.2). 115 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 折笠精一, 福崎篤: "小児泌尿器科学書" 川村猛,小柳知彦編,金原出版、東京, 117-123 (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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