2007 Fiscal Year Final Research Report Summary
The point mutation of polymeric immunoglobulin receptor and IgA nephropathy
| Project/Area Number |
18592071
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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 |
Pathobiological dentistry/Dental radiology
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| Research Institution | Nihon University |
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Principal Investigator |
ASANO Masatake Nihon University, School of Dentistry, Assistant Professor (10231896)
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| Project Period (FY) |
2006 – 2007
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| Keywords | pIgR / IgA nephrop athy / point mutation / free secretory component |
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| Research Abstract |
Comparison of the genomic DNA sequences of the peripheral blood samples taken from healthy individuals and IgA-nephropathy (IgAN) patients has revealed that, in IgAN-patients, high-score DNA mutation was detected in polymeric immunoglobulin receptor (pIgR) DNA. The mutation was frequently detected at the position of 580 aa and resulted in the substitution of alanine to valine residue. The aim of this study was to compare the biochemical properties of wild type and mutant pIgR (A580V) molecules and to elucidate the correlation of this mutation to IgAN. Both cDNA was introduced into mammalian expression vector and used for transfection. Both transfectants were labeled by metabolic labeling or surface biotinylation methods. After labeling, the amount of free secretory component (fSC ; the extracellular part of pIgR) released in the culture medium was estimated. However, no differences were observed between wt and mutant. The glutamic acid in the positions 606 and 607 were known to be conserved between several animal species and thought to be a cleaving site of the exrtracellular portion of pIgR. By substituting these two residues to alanine residue with site-directed mutagenesis, we examined the influence of these changes on the release of fSC. As results, no changes were observed. These results suggested that enzymatic cleavage of pIgR might be differentially. controlled between epithelial and fibroblastic cells.
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