| Project/Area Number |
14571026
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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 | The University of Tokushima |
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Principal Investigator |
TSUKAGUCHI Hiroyasu The University of Tokushima, School of Medicine, Instructor, 医学部, 助手 (60335792)
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| Co-Investigator(Kenkyū-buntansha) |
NOMA Yoshihiko The University of Tokushima, University Hospital, Associate Professor, 医学部・歯学部附属病院, 講師 (10218349)
KUWAJIMA Masamichi The University of Tokushima, School of Medicine, Associate Professor, 医学部, 助教授 (00205262)
DOI Toshio The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (60183498)
NAKAYA Yutaka The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (50136222)
MIZUNO Akira The University of Tokushima, University Hospital, Instructor, 医学部・歯学部附属病院, 助手 (80219641)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | kidney / gene / nephrotic syndrome / renal failure / podocyte / ポドドサイト / ゲノム / 遺伝子変異 / ネフローゼ症候群 / 腎糸球体上皮 |
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| Research Abstract |
Nephrotic syndrome is characterized by a massive proteinuria and is caused by functional or/and structural disruption of slit membrane, which connects adjacent podocyte foot processes and serves as a glomerular filtration barrier. Recent advance in human molecular genetics shed light on the mechanism underlying nephrotic syndrome and showed that defects in nephrin (NPHS1) and podocin (NPHS2), both of which are expressed in the slit diaphragm, are responsible for early onset nephrotic syndrome.
To understand the role of podocin in the pathogenesis, we analyzed podocin localization by using rat PAN-induced nephrotic model and transfected cells stably expressing podocin (mouse L cell and MDCK). In podocytes of PAN treated rats, podocin was recruited from the slit diaphragm to the newly formed cell junctions. Consistent with this finding, we observed accumulation of podocin into cell-cell junctions of stably transfected cells. The presence of podocin at cell-cell junctions, including normal slit membrane as well as PAN-induced tight junction, suggested that the role of podocin is to provide a scaffold that allows efficient accumulation of molecules, which is necessary to form stable cellular junctions.
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