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Functional Molecules on Glomerular Epithelial Cells

Research Project

Project/Area Number 08044260
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionNiigata Univeisity

Principal Investigator

SHIMIZU Fujio  Niigata Unlv.Sch.Med., Professor, 医学部, 教授 (40012728)

Co-Investigator(Kenkyū-buntansha) KAWACHI Hiroshi  Niigata Unly.Sch.Med., Assoclate Professor, 医学部, 助教授 (60242400)
MORIOKA Tetsuo  Niigata Unlv.Sch.Med.Associate Professor, 医学部, 助教授 (00210146)
SHIA Michael A  Boston Unlv.Sch.Med., Associate Professor, 医学部, 助教授
SALANT David J  Boston Unlv.Sch.Med.Professor, 医学部, 教授
Project Period (FY) 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1996: ¥2,600,000 (Direct Cost: ¥2,600,000)
Keywordsp51 / ZO-1 / proteinuria / slit membrane / tyrosine phosphorylation / glomerular permeability / monoclonal antibody
Research Abstract

cDNA library was prepar from one day old rat glomeruli, because the metabolic labeling by ^<35>S-methyonine revealed that mAb 5-1-6 recognized antigen (p51) was more actively synthesized in one day old rat kidney than in 5 days old or matured rat kidneys. cDNA cloning by mAb 5-1-6 is being still continued using this library and COS cells for expression. However we have not yet succeeded in identifying p51.
On the other hand the precise localization of p51 was further investigated with immunoelectron microscopy by counting the gold particles. The number of gold particles at the base of foot processes of podocytes is 0.77 particles/mm length of glomerular basement membrane. of particles at the lateral surface and at intermittent space of foot processes are 1.61 and 2.14, respectively.From these results we concluded that p51 is mainly localized at the slit diaphragm and its cytoplasmic face and that p51 is a component of slit diaphragin.
To clarify the mechanisms of abnormal proteinuria induced by mAb 5-1-6, we have investigated the molecular nature of slit diaphragm. Any morphological alterations of the structure of slit diaphragm was not detected with electron microscopy in proteinuric rats induced by mAb 5-1-6. However, p51 and ZO-1, tight junction protein, staining were definitely decreased at glomeruii of rats 5 days after mAb injection when abnomal proteinuria reached a peak value. lmmunoblot analysis also showed that intensity of ZO-1 band was decreased at glomeruii of 5 days after mAb injection. From these results we conchuded that p51 is an associate protein of ZO-1 and that these proteins are not necessary for maintaining the structure of slit diaphragm but necessary for maintaining the barrier function of slit diaphragm.
We have further investigated whether tyrosine phosphorylation plays a role for this molecular rearrangement of p51 and ZO-1. Tyrosine phosphorylation was not detected at any time points after mAb 5-1-6 injection.

Report

(2 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Kitamura M: "Transforming grtowth factor-β1 is the predominant paracrine inhibitor of macrophage cytokine synthesis produced by glomelular mesangial cells" J.Immunol. 156. 2964-2971 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fujigaki,Y: "Structural continuity of filtration slit (slit diaphrgm) to plasma membrane of podocyte" Kidney Int. 50. 54-62 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Narisawa-Saito-M: "Thy-1 mediated phosphatidylinositol turnover in cultured rat glomerular mesangial cell" J.Cell Physiol. 168. 705-710 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Narisawa-Saito-M: "Thy-1 molecule associates with protein tyrosine kinases in rat mesangial cells" Clin Exp Immunol. 106. 86-90 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Orikasa M: "Macrophagic cells outgrowth from normal rat glomerular culture : passible metaplastic change from podocytes" Lab Invest. 75. 719-733 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Lip: "Suppressive effects of Sairei-to on mAb 1-22-3 induced glomerulonephritis : Analysis of effective components" Pathol Int. (印刷中). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Salant D: "Immunologic renal diseases" Lippincott-Raven, 1258 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kitamura M: "Transforming growth factor-BETA 1 is the predominant paracrine inhibitor of macrophage cytokine synthesis produced by glomeluar mesangial cells" J.Immunol. 156. 2964-2971 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Fujigaki Y: "Stractural continuity of filtration slit (slit diaphragm) to plasma membrane of podocytes" Kidney Int. 50. 54-62 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Narisawa-Saito-M: "Thy-1 mediated phosphatidy linositol turnover In cultured rat glomerular mesangial cell" J.Cell physiol. 168. 705-710 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Narisawa-Saito M: "Thy-1 molecule associates with protein tyrosine kinases in rat mesangial cells" Clin Exp Immunol. 106. 86-90 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Orikasa M: "Macrophagic cells outgrowth from normal rat glomerular culture : possible metaplastic change from podocytes" Lab Invest. 75. 719-733 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Li P: "Suppressive effects of Sairei-to on mAb 1-22-3 induced glomerulonephritis : Analysis of ettective components" Pathol Int. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Salant D: Glomerular Injury Due to Antibody Alone. Llppincott-Raven, 359-375 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kitamura M: "Transforming grtowth factor-β1 is the predominant paracrine inhibitor of macrophage cytokine synthesis produced by glomelular mesangial cells" J.Immunol. 156. 2964-2971 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Fujigaki,Y: "Structural continuity of filtration slit(slit diaphrgm)to plasma membrane of podocyte" Kidney Int. 50. 54-62 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Narisawa-Saito-M: "Thy-1 mediated phosphatidylinositol turnover in cultured rat glomerular mesangial cell" J.Cell Physiol. 168. 705-710 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Narisawa-Saito-M: "Thy-1 molecule associates with protein tyrosine kinases in rat mesangial cells" Clin Exp Immunol. 106. 86-90 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Orikasa M: "Macrophagic cells outgrowth from normal rat glomerular culture:passible metaplastic change from podocytes" Lab Invest. 75. 719-733 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] LiP: "Suppressive effects of Sairei-to on mAb 1-22-3 induced glomerulonephritis:Analysis of effective components" Pathol Int. (印刷中). (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Salant D: "Immunologic renal diseases" Lippincott-Raven, 1258 (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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