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Molecular mechanisms on the mesangial cell activation by IgA nephropathy-associated antigens.

Research Project

Project/Area Number 05670965
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Kidney internal medicine
Research InstitutionJikei University School of Medicine

Principal Investigator

SAKAI Osamu  Jikei University School of Medicine, Professor, 医学部, 教授 (40056560)

Co-Investigator(Kenkyū-buntansha) NAGASAWA Ryuji  Saitama Medical Center, Lecturer, 医学部, 講師 (70146794)
UTSUNOMIYA Yasunori  Jikei University School of Medicine, Assistant, 医学部, 助手 (70231181)
KAWAMURA Tetsuya  Jikei University School of Medicine, Lecturer, 医学部, 講師 (20161367)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥1,700,000 (Direct Cost: ¥1,700,000)
KeywordsIgA Nephropathy / Tyrosine Kinase / Cultured Mesangial Cells / RT-PCR / Flt-1 / PDFG / Thymectomy / IgA Deposition / メサンギウム細胞 / IgA免疫複合体
Research Abstract

1. Identification and characterization of tyrosine kinases expressed in glomerular cells.
We isolated and identified the tyrosine kinase genes by RT-PCR with degenerate primers from messenger RNA prepared from isolated glomeruli, cultured mesangial cells and cultured glomerular endthelial cells. Sequence analysis of PCR-amplified cDNAs resulted in the isolation of 24 tyrosine kinases. We showed for the first time the constitutive expression of 15 tyrosine kinases ; tyro-1, tyro-4, tyro-6, hyk, Ptk-3, Ryk, tie, yes, lyn, tec, Jak1, Jak2, Jak3, c-abl, and flk, in renal glomeruliin addition to the previously known renal expressions of 7 tyrosine kinases ; IGFR,Trk B,PDGFR,Flt-1, Flk-1, bFGFR,and Ufo.
2.Functional role of Flt-1 expressed in glomerular mesangial cells.
We showed that, Flt-1, an endothelial cell-specific receptor-type tyrosine kinase for vascular endotherial growth factor (VEGF), is expressed in renal mesangial cells. We further investigated its gene expression in cultured mesangial cells upon the stimulation of PDGF with the concomitant up-regulation of VEGF.These data suggest the possible involvement of VEGF/Flt-1 system in cytokine-induced mesangial cell proliferations.
3.Neonatal thymectomy diminished renal IgA deposition in IgA nephropathy-prone ddY mice.
To clarify the role of T cells on mesangial IgA deposition in the kidney of ddY mice, we investigated the IgA deposition in neonatally thymectomized ddY mice. Although the thymectomized mice developed a renal lesion closely resembling that typical of IgAN,the extent of their mesangial IgA deposition was significantly milder than in control sham-operated mice. The percentage of splenic T cells and the magnitude of mitogenic responses both decreased markedly in thymectomized compared with control mice. The results suggest that thymus-derived T cells or their products determine the amount of IgA deposition in the kidney of ddY mice.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Kitamura A,et al.: "Renal fibroblasts are sensitive to growth-repressing and matrix-reducing factors from activated lymphocytes." Clin Exp Immunol. 91. 516-520 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 酒井 紀: "IgA腎症の成因と治療" 日本腎臓学会誌. 36. 683-691 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagasawa R, et al.: "Neonatal thymectomy diminishes renal lgA deposition in IgA nephropathy-prone ddY mice." Nephron. 66. 326-332 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Utsunomiya Y et al.: "Attenuation of immune complex nephritis in NZB/WF1 mice by a prostacyclin analogue." Clin Exp Immunol. 99. 454-457 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahashi T, et al.: "Protein'Tyrosine Kinases Expressed In Glomeruli and Cultured Glomerular Cells:Flt-1 and VEGF Expression in Renal Mesangial Cells." Biochem Biophys Res Commun. (In Press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagasawa R, et al.: "Polymorphism of the T-cell receptor b chain gene and the prognosis of IgA nephropathy in Japanese patients." Nephron. (In Press). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kitamura A,et al.: "Renal fibroblasts are sensitive to growth-repressing and matrix-reducing factors from activated lymphocytes." Clin Exp Immunol. 91. 516-520 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sakai O.: "Pathogenesis and therapy of IgA nephropathy." Jpn J Nephrol. 36. 683-691 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagasawa R,et al.: "Neonatal thymectomy diminishes renal IgA deposition in IgA nephropathy-prone ddY mice." Nephron. 66. 326-332 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Utsunomiya Y,et al.: "Attenuation of immune complex nephritis in NZB/WF1 mice by a prostacyclin analogue." Clin Exp Immunol. 99. 454-457 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahashi T,et al.: "Protein Tyrosine Kinases Expressed In Glomeruli and Cultured Glomerular Cells : Flt-1 and VEGF Expression in renal Mesangial Cells." Biochem Biophys Res Commun. (in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Nagasawa R,et al.: "Polymorphism of the T-cell receptor b chain gene and the prognosis of IgA nephropathy in Japanese patients." Nephron. (in press). (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kitamura A,et al.: "Renal fibroblasts are sensitive to growth-repressing and matrix-reducing factors from activated lymphocytes." Clin Exp Immunol. 91. 516-520 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] 酒井紀: "IgA腎症の成因と治療" 日本腎臓学会誌. 36. 683-691 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nagasawa R,et al.: "Neonatalthymectomy diminishes renal IgA deposition in IgA nephropathy-prone dd Y mice." Nephron. 66. 326-332 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Utsunomiya Y,et al.: "Attenuation of immune complex nephritis in NZB/WFl mice by a prostacyclin analogue." Clin Exp Immunol. 99. 454-457 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takahashi T,et al.: "Protein Tyrosine Kinases Expressed In Glomeruli and Cultured Glomerular Cells:Flt-1 and VEGF Expression in Renal Mesangial Cells." Biochem Biophys Res Commun. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Nagasawa R,et al.: "Polymorphism of the T-cell receptor b chain gene and the prognosis of IgA nephropathy in Japanese patients." Nephron. (in press). (1995)

    • Related Report
      1994 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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