Basic study for molecular mechanisms and novel therapy of Alport syndrome
| Project/Area Number |
20591273
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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 | Niigata University |
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Principal Investigator |
KOBAYASHI Takehiro Niigata University, 医歯学系, 准教授 (90311670)
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| Co-Investigator(Kenkyū-buntansha) |
UCHIYAMA Makoto 新潟大学, 医歯学系, 教授 (80108050)
IKEZUMI Yohei 新潟大学, 医歯学総合病院, 講師 (70361897)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | アルポート症候群 / IV型コラーゲン / ヘテロ三量体 / HSP47 / NC1ドメイン / コラーゲンドメイン / 変異 / NClドメイン / IV型コラーゲンα鎖 |
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| Research Abstract |
Alport syndrome (AS), or progressive hereditary nephritis, is caused by mutations in type IV collagen α3, α4, and α5 chains. In this study, we introduced a variety of AS mutations into the α5(IV) chain and characterized the resulting mutants. The results showed that a defect in the hetrotrimer formation of α3(IV), α4(IV), and α5(IV) chains and/or a defect in secretion of the heterotrimer from cells, is the major molecular mechanism that defines the pathogenesis of AS. In contrast to these findings, other studies have demonstrated that some mutant α5(IV) chains form the heterotrimer in the correct conformation, suggesting the involvement of other molecular mechanisms. Moreover, we elucidated that molecular chaperone HSP47 plays a critical role in heterotrimerization of the three chains.
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Report
(4 results)
Research Products
(12 results)
