THE ROLE OF FRAGMENTED FIBRONECTIN IN THE MESANGIAL IGA-DEPOSITION AND PROLIFERATION IN IGA NEPHROPATHY.
| Project/Area Number |
07670833
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | HIROSAKI UNIVERSITY |
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Principal Investigator |
WAGA Shinobu HIROSAKI UNIVERSITY SCHOOL OF MEDICINE ASSOCIATE PROFESSOR, 医学部, 助教授 (10167744)
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| Co-Investigator(Kenkyū-buntansha) |
KAKIZAKI Yoshiki HIROSAKI UNIVERSITY SCHOOL OF MEDICINE,HOSPITAL ASSISTANT PROFESSOR, 医学部附属病院, 講師 (40160973)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1996: ¥200,000 (Direct Cost: ¥200,000)
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| Keywords | IgA nephropathy / matrix-assembly / C-terminal fragmented fibronectin / fragmented fibronectin / IgA-fibronectin complex / フィブロネクチン / IgA |
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| 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.
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Report
(3 results)
Research Products
(14 results)
