2004 Fiscal Year Final Research Report Summary
Mechanism of proteinuria resulted from the dysfunction of podocyte slit diaphragm
| Project/Area Number |
14370317
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Niigata University |
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Principal Investigator |
KAWACHI Hiroshi Niigata University, Graduate School of Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (60242400)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Fujio Niigata University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (40012728)
KOIKE Hiroko Niigata University, Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (90323964)
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| Project Period (FY) |
2002 – 2004
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| Keywords | proteinuria / podocyte / slit diaphragm / nephrin / podocin / NEPH1 / CD2AP / IP-10 |
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| Research Abstract |
Our group has been studying the molecular composition of slit diaphragm(SD) of podocyte that is accepted to be a critical structure for maintaining the barrier function of glomerular capillary wall. In this project, we analyzed the molecular composition of the SD. In the first year of this project (2002), we analyzed the nature of the SD-associated molecules, podocin, CD2AP and ZO-1. In the second year (2003), we cloned a rat homologue of NEPH1 and analyzed its molecular nature. In the final year (2004), we analyzed the interaction of these SD associated molecules with nephrin. In addition, we tried to identify other important molecules of the SD. We detected that podocin is expressed not only in podocyte but also in astrocyte in brain, which suggested that podocin play a role in regulating the function of blood-brain barrier as well as in glomerular capillary wall. We observed that the expression of podocin, CD2AP, ZO-1, and NEPH1 is altered in proteinuric states. We showed that the interactions of nephrin-podocin and nephrin-CD2AP are dissociated at the onset of proteinuria. We also demonstrated that interferon-inducible protein 10 is expressed in podocyte and play a role in regulating the expression of the SD-associated molecules. We published these findings as manuscripts in the top journals of Nephrology field, Kidney International and Journal of American Society of Nephrology. We reported some results at the annual meeting of the American Society of Nephrology held in San Diego (2003) and St.Rouis (2004). We are convinced that the results obtained in this project contributed to the better understanding the pathogenic mechanism of proteinuria and to establishment for the novel therapy.
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Research Products
(76 results)
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[Journal Article] Expression and regulation of adrenomedullin in renal glomerular podocytes.2005
Author(s)
Hino M, Nagase M, Kaname S, Shibata S, Nagase T, Oba S, Funaki M, Kobayashi N, Kawachi H, Mundel P, Fujita T.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Novel expression of sodium/myo-inositol co-transporter in pdoocytes in puromycin aminonucleoside nephrosis.2004
Author(s)
Watanabe Y, Kobayashi T, Yaoita E, Kawachi H, Yamauchi a, Inoue T, Shimizu F, Yoshida Y, EI-Shemi AG, Okada H, Suzuki H, Yamamoto T.
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Journal Title
Nephrol Dial Transplant 19
Pages: 817-822
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Prevention and reversal of renal injury by leptin in a new mouse model of diabetic nephropathy.2004
Author(s)
Suganami T, Mukoyama M, Mori K, Yokoi H, Koshikawa M, Sawai K, Hidaka S, Ebihara K, Tanaka T, Sugawara A, Kawachi H, Vinson C, Ogawa Y, Nakao K.
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Journal Title
FASEB Journal 19
Pages: 127-129
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Role of megalin in endocytosis of advanced glycation end products : Implications for a novel protein binding to both megalin and advanced glycation end products.2003
Author(s)
Saito A, Nagai R, Tanuma A, Hama H, Cho K, Takeda T, Yoshida Y, Toda T, Shimizu F, Horiuchi S, Gejyo F.
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Journal Title
J Am Soc Nephrol. 14
Pages: 1123-1131
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Bioengineered implantation of megalin-expressing cells : A potential intracorporeal therapeutic model for uremic toxin protein clearance in renal failure.2003
Author(s)
Saito A, Kazama J.J, Iino N, Cho K, Sato N, Yamazaki H, Oyama Y, Takeda T, Orlando R.A, shimizu F, Tabata Y, Gejyo F.
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Journal Title
J Am Soc Nephrol. 14
Pages: 2025-2032
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Genetic polymorphism of NPHS1 modifies the clinical manifestations of Ig A nephropathy.2003
Author(s)
Narita I, Goto s, Saito N, Song J, Kondo D, Omori K, Kawachi H, Shimizu F, Sakatsume M, Ueno M, Gejyo F.
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Journal Title
Lab Invest. 83
Pages: 1193-1200
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Hydrodynamics-based delivery of the viral interleukin-10 gene suppresses experimental crescentic glomerulonephritis in Wistar-Kyoto rats.2003
Author(s)
Higuchi N, Maruyama H, Kuroda T, Kameda S, Iino N, Kawachi H, Nishikawa Y, Hanawa H, Tahara H, Miyazaki J, Gejyo F.
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Journal Title
Gene Ther. 10
Pages: 1297-1310
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Therapeutic effect of sulphated hyaluronic acid, a potential selectin-blocking agent, on experimental progressive mesangial proliferative glomerulonephritis.2002
Author(s)
Matsuda M, Shikata K, Shimizu F, Suzuki Y, Miyasaka M, Kawachi H, Kawashima H, Wada J, Sugimoto H, Shikata Y, Ogawa D, Tojo S.J, Akima K, Makino H.
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Journal Title
J Pathol 198
Pages: 407-414
Description
「研究成果報告書概要(欧文)」より
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[Book] 腎臓ナビゲーター2004
Author(s)
河内 裕
Total Pages
303
Publisher
メディカルレビュー社
Description
「研究成果報告書概要(和文)」より
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