The Analysis of aberrant glycosylation of IgA and B cells secreting those IgAs in IgA Nephropathy
| Project/Area Number |
25461232
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Juntendo University |
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Principal Investigator |
KIHARA Masao 順天堂大学, 医学部, 助教 (50512604)
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| Co-Investigator(Kenkyū-buntansha) |
TOMINO Yasuhiko 順天堂大学, 医学部, 教授 (60130077)
SUZUKI Hitoshi 順天堂大学, 医学部, 准教授 (10468572)
SUZUKI Yusuke 順天堂大学, 医学部, 准教授 (70372935)
NAKATA Junichiro 順天堂大学, 医学部, 助教 (20365638)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | IgA腎症 / 糖鎖不全 / 糖鎖不全IgA / ハイブリドーマ |
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| Outline of Final Research Achievements |
O-linked glycans of IgA1 from IgAN patients revealed an aberrant glycosylation status characterized by diminished galactosylation. Implantation of transfectoma cells secreting an IgA derived from ddY mice (ddY-IgAN hybridoma) induced glomerular lesion resembling human IgAN in BALB/c mice. Among the six GalNAc-Ts expressed in human B cells, GalNAc-T2 exhibited the highest catalytic activity in transferring GalNAc to a synthetic peptide from the hinge region of human IgA1. We observed that GalNAc-T2 mRNA expression was higher in ddY-IgA N hybridoma than ddY-deriver hybridoma not inducing IgAN. Thus, more O-glycosylated ddY-IgAN hybridoma will be generated by either enhancing the expression of GalNAc-T2 through transfection with plasmids encoding GalNAc-T2 cDNA. The extent of O-glycosylation from the hinge region of secreted IgAs will be verified by MALDI-TOF MS, and cells secreting ddY-IgAN hybridoma variants will be implanted into BALB/c mice to test their nephritogenicity.
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Report
(4 results)
Research Products
(2 results)
