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THE ROLE OF FRAGMENTED FIBRONECTIN IN THE MESANGIAL IGA-DEPOSITION AND PROLIFERATION IN IGA NEPHROPATHY.

Research Project

Project/Area Number 07670833
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionHIROSAKI UNIVERSITY

Principal Investigator

WAGA Shinobu  HIROSAKI UNIVERSITY SCHOOL OF MEDICINE ASSOCIATE PROFESSOR, 医学部, 助教授 (10167744)

Co-Investigator(Kenkyū-buntansha) KAKIZAKI Yoshiki  HIROSAKI UNIVERSITY SCHOOL OF MEDICINE,HOSPITAL ASSISTANT PROFESSOR, 医学部附属病院, 講師 (40160973)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1996: ¥200,000 (Direct Cost: ¥200,000)
KeywordsIgA nephropathy / matrix-assembly / C-terminal fragmented fibronectin / fragmented fibronectin / IgA-fibronectin complex / フィブロネクチン / IgA
Research Abstract

Backgrounds
Immunoglobulin A (IgA) deposition in the glomerular mesangial matrix is a prerequisite for the diagnosis of IgA nephropathy, and circulating IgA-containing complex has been implicated in this process. Composition of these complexes has been extensively studied, but fragmented fibronectin has not been reported. Since fragmented fibronectin by itself is known to be involved in the assembly of extracellular matrix, we investigated whether fragmented fibronectin exists in patient's serum and is capable of binding IgA.
Methods
Serum from patients with IgA nephropathy was applied to heparin-affinity column and the effluent was analyzed by Western-blot technique with a set of anti-human fibronectin monoclonal antibodies. Native fibronectin was digested with cathepsin D to obtain fragment similar to that of serum fibronectin, and the capacity of fibronectin to bind IgA was modeled with a mixture ofpurified IgA1 and cathepsin D-digested fibronectin using affinity purification on jacalin-agarose.
Findings
A fragment at about 43 kDa reacted only in the patients with antibody FN 1-1, which is specific to the carboxyl-terminal region of fibronectin containing a disulfide bond. A similar-sized fragment was generated by cathepsin D-digestion of the native molecule and was bound to IgA1 in vitro.
Interpretation
This study demonstrates that about a 43 kDa carboxylterminal fragment of fibronectin was able to bind IgA1 and a fragment of similar size was present in patients'sera. Since the carboxyl-terminal disulfide bond is known to be critical in assembling exogenous fibronectin into the extracellular matrix, the affinity of IgA1 to a fragment found in patients may have pathogenic potential to participate in extracellular expansion and IgA-deposition in IgA nephropathy.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Waga, S. et al.: "Frgmentation of Fibronectin in the serum from IgA nephropathy and binding of IgA1 to fragmented fibronectin." J. Am. Soc. Mephrol.6. 931- (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kakizaki, Y. et al.: "Production of monocyte chemoastnutant protein-1 by bouneglomerular enolotheliod cells." Kidney Int.48. 1866-74 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Waga, S. et al.: "IgA nephropathy in a patient with loterd renal agenesis." Nephron. 74. 479-480 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tanaka H, et al.: "Capacity of H_2O_2 nelease from monocytes in steroid-sensitive nephrotic syndrome." Tohoku J. exp. med.178. 271-277 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] WAGA,S.ET AL.: "FRAGMENTATION OF FIBRONECTIN IN THE SERUM FROM IGA NEPHROPATHY AND BINDING OF IGA1 TO FRAGMENTED FIBRONECTIN." J AM SOC NEPHROL. 6. 931 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] KAKIZAKI,Y AND WAGA,S ET AL.: "PRODUCTION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 BY BOVINE GLOMERULAR ENDOTHELIAL CELLS" KIDNEY INT. 48. 1866-74 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] WAGA,S.ET AL.: "IGA NEPHROPATHY IN A PATIENT WITH UNILATERAL RENAL AGENESIS." NEPHRON. 74. 479-480 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] TANAKA,H AND WAGA,S ET AL.: "CAPACITY OF H202 RELEASE FROM MONOCYTES IN STEROID-SENSITIVE NEPHROTIC SYNDROME." TOHOKU J EXP MED.178. 271-277 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Waga,S.et al.: "IgA nephropathy in a patient with unilateral renal agenesis." Nephron. 74. 479-480 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka,H.and Waga,S.et al.: "Capacity of H_2O_2 release from monocytes in stersid sensitive nephotic syndrome." Tohoku J.Exp.Med.178. 271-277 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tanaka,H.and Waga,S.et al.: "An adolescent case of anti-neutnophil cytoplasmic autoantibodies-associated cresecntic glomerulonephritis with subclinicalautionmune thyroidits." Japanese J.Nephrol.38(10). 463-468 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Waga,S: "Fragmentation of fibronectin in the serum from IgA nephropathy and binding of IgA,fagmented fibronectine." J.Am.Soc.Nephrol. 6. 931 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Waga,S: "IgA nephropathy in a patient with unilateral renalagenesis" Nephron. (印刷中). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tanaka,H: "Capaciyty of H_2O_2 release from monocytes in steroid-sensitive nephrotic syndrome" Tohoku J.Exp.Med.(印刷中). (1996)

    • Related Report
      1995 Annual Research Report

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

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