• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

REGULATION OF TGF-β AND ITS SIGNAL MOLECULE, SMAD FOR ATTENUATION OF PERITONEAL FIBROSIS.

Research Project

Project/Area Number 12671058
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionKurume University

Principal Investigator

KOHNO Keisuke  KURUME UNIVERSITY SCHOOL OF MEDICINE, DEPARTMENT OF NEPHROLOGY, ASSISTANT PROFESSOR, 医学部, 助手 (70258416)

Co-Investigator(Kenkyū-buntansha) OKUDA Seiya  KURUME UNIVERSITY SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (80158823)
TAMAKI Kiyoshi  KURUME UNIVERSITY SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (10312141)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsGrowth factor / TGF-β / Smad / peritoneal fibrosis / Adenovirus-vector / CAPD / Smad binding element / 細胞外マトリックス / 線維化 / 遺伝子導入
Research Abstract

TGF-β1 plays a pathological role in fibrotic and sclerotic diseases including peritoneal fibrosis. Smads have been identified as pivotal components in TGF-** intracellular signaling. The present study was carried out to investigate TGF-β-induced Smad activation in cultured cells and experimental peritoneal firotic diseases in rodents. In cultured! cells, TGF-β1 induced phosphorylation of Smad2.Gene transfer using Adenovirus-vector, double-overexpression of Smad2 and Smad4 induced TGF-I3istimulated plasminogen activator inhibitor-1 (PM-i) expression more than overexpression of each Smad alone. Furthermore, overexpression of Smad7, one of inhibitory Smads, but not Smd6 reversed TGF- β1-inhibited cell proliferation by inhibiting Smad2 phosphorylation. In addition, TGF-β1 or high glucose condition induced the expression of SBE (Smad-binding element)-luciferase activity, which was reversed by the transfection-with Smad2 mutant or inhitory Smad7.
In experimental peritoneal fibrosis using iodine, progressive peritoneal thickness was observed. This thickness was due to the accumulation of matrix proteins. We tried gene transfer of Smad protein into these animal models. But the peritonea! fibrosis was not reproducible. We are now under investigation to make reproducible model of peritoneal fibrosis. However, our results indicate the possibility that modulation of Smad activity may attenuate the development of peritoneal fibrosis and sclerosis.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Ueda S, Kono K, et al.: "Overexpression of Smad7 not Smad6 inhibits TGF-b actions in mesangial cells"A.J.Soc.Nephrol.. 623A. (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Haramaki R, Tamaki K, et al.: "Steroid therapy and urinary transforming growth factor-betal in IgA nephropathy"Am.J.Kidney.Dis.. 38(6). 1191-1198 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kato S, Tamaki K, et al.: "Ectopic expression of Smad7 inhibits transforming growth factor-beta responses in vascular smooth muscle cells"Life Sci.. 69,22. 2641-2652 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tamaki K, et al.: "Chinese herbs nephropathy : a variant form in Japan"Intern Med.. 40(4). 267-268 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tamaki K, Okuda S;: "Role of TGB-β in the progression of renal fibrosis"Indian review of renal fibrosis. (印刷中). (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 玉置清志: "糸球体病変と成長因子、ケモカイン"内科. 87(6). 1211-1217 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 奥田誠也: "腎と透析、51、臨時増刊"糖尿病性腎症におけるTGF-βの役割. 162-167 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tamai O, Tamaki K, Okuda S et al: "Caveolae in mesangial cells and caveolin expression in mesangial proliferative glomerulonephritis."Kidney Int.. 59. 471-480 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Haramaki R, Tamaki K. et al.: "Steroid therapy and urinary transforming growth factor-betal in IgA nephropathy."Am J Kidney Dis.. 38. 1191-1198 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kashiwagi M, S Tamaki K.et al: "Locally activated reninangiotensin system associated TGF-β1 as a major factor for renal injury induced by chronic inhibition of nitric oxide synthase in rats."J Am Soc Nephrol. 11. 616-624 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kato S, Tamaki K. et al.: "Ectopic expression of Smad? inhibits transforming growth factor-beta responses in vascular smooth muscle cells"Life Sci. 69. 2641-2652 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ueda S, Kohno K, et al: "Overexpression of Smad7 not Smad6 inhibits TGF-β actions in mesangial cells"J A Soc Nephrol. 12. 623A (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Haramaki R, Tamaki K. Okuda S et al: "Steroid therapy and urinary transforming growth factor-b1 in IgA nephropathy."J Am Soc Nephrology. 11. 62 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ueda S, Kono K, et al.: "Overexpression of Smad7 not Smad6 inhibits TGF-b actions in mesangial cells"A J Soc Nephrol. 623A. (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Haramaki R, Tamaki K, et al.: "Steroid therapy and urinary transforming growth factor-betal in IgA nephropathy"Am J Kidney Dis.. 38(6). 1191-1198 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kato S, Tamaki K, et al.: "Ectopic expression of Smad7 inhibits transforming growth factor-beta responses in vascular smooth muscle cells"Life Sci.. 69(22). 2641-2652 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tamaki K, et al.: "Chinese herbs nephropathy : a variant form in Japan"Intern Med.40(4). 267-268 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tamaki K, Okuda S: "Role of TGB-β in the progression of renal fibrosis"Indian review of renal fibrosis. (印刷中).

    • Related Report
      2001 Annual Research Report
  • [Publications] 玉置清志 他: "糸球体病変と成長因子、ケモカイン"内科. 87(6). 1211-1217 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 奥田誠也 他: "腎と透析、51、臨時増刊"糖尿病性腎症におけるTGF-βの役割. 162-167 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kohno K, et al: "Depressor effect by exercise training is associated with amelioration of hyperinsulinemia and sympathetic overactivity."Intern Med.. 39(12). 1013-9 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kohno K, et al: "Minimal change nephrotic syndrome associated with rifampicin treatment"Nephrol Dial Transplant.. 15(7). 1056-9 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kohno K, et al: "A case of normotensive scleroderma renal crisis after high-dose methylprednisolone treatment"Clin Nephrol.. 53(6). 479-82 (2000)

    • Related Report
      2000 Annual Research Report

URL: 

Published: 2000-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi