1999 Fiscal Year Final Research Report Summary
Molecular biological analysis for the responsible antigen of membranous nephropathy
| Project/Area Number |
10671009
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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 |
Kidney internal medicine
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| Research Institution | Teikyo University |
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Principal Investigator |
MATSUI Katsuyuki Teikyo University, Medicine, Assistant Professor, 医学部, 助手 (20256027)
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| Co-Investigator(Kenkyū-buntansha) |
NAGASE Mitsumasa Teikyou University, Medicine, Professor, 医学部, 教授 (00010124)
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| Project Period (FY) |
1998 – 1999
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| Keywords | protein uria / glomerulus / Nephritis / basement membrane / epithelial cell / podoplanin / integral membrane |
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| Research Abstract |
Membranouns nephropathy is one of the autoimmune diseases, but its responsible antigen(s) is still unclear except some such as a hepatitis B virus. There are two types of membranous nephropathy, which are primary and secondarily. It is widely known that the tumor associated membranous nephropathy as the latter, and that the tumor associated neoantigen may be the pathogenic antigen, but the precise antigen from tumor is not identified. Heymann nephropathy is well documented as an animal model of membranous nephropathy, its antigen is clarified as gp330 and its amino acid sequence named as Megarin was defined. But this antigen is not expressed in human tissue, therefore the importance of the identification of human membranous nephropathy increased. The facts that the antigenic epitope is located at glomerular epithelial cell in Heymann nephropathy and that the membranous nephropathy is believed as an autoimmune disease, strongly indicate the pathogenic antigen for human membranous nephropathy may exist on epithelial cells. We have established the methods for purifying the integral membrane from glomeruli by using high pH buffer and non-ionic detergent. The purified integral membrane from glomeruli was use for immunogen for establishing monoclonal antibodies. The monoclonal antibody reacted the 43kD glycoprotein and the antigen located the surface of epithelial cells. The amino acid sequence was identified and named as Podoplanin. Anti Podoplanin antibody induced the massive protein uria in rats and the effacement of podocytes. These results arise the question of the status of Podoplanin in human membranous nephropathy.
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