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Analysis on the mechanism of proteinuria induced by glomerular epithelial cell lesions

Research Project

Project/Area Number 13470210
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionNIIGATA UNIVERSITY

Principal Investigator

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)

Co-Investigator(Kenkyū-buntansha) YAOITA Eishinn  Graduate School of Medical and Dental Sciences Associate Professor, 大学院・医歯学総合研究科, 助教授 (00157950)
KAWACHI Hiroshi  Graduate School of Medical and Dental Sciences Associate Professor, 大学院・医歯学総合研究科, 助教授 (60242400)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2002: ¥5,800,000 (Direct Cost: ¥5,800,000)
Keywordsproteinuria / glomerular epithelial cell / slit membrane / nephrin / nephrotic syndrome
Research Abstract

We have succeeded in cloning the rat homologue of nephrin which is a product of gene responsible for Finnish-type congenital nephrotic syndrome and concluded that proteinuria-inducing monoclonal anti-rat slit membrane antibody 5-1-6 recognizes the extracellular sites of rat nephrin. In 5-1-6 nephropathy, induced by a single injection of 5-1-6, and also in PAN nephrosis, representative rat model for nephrotic syndrome, the expression of nephrin was decreased already in early stage before start of proteinuria, which suggested that the decrease of nephrin expression is not the result but cause of proteinuria and nephrin abnormality is intimately related not only to congenital but also acquired renal lesions, especially the induction of proteinuria.
We have succeeded also in cloning the recently reported podocin, a product of gene responsible to familial FSGS. In 5-1-6 nephropathy as well as in PAN nephrosis immunofluorescent positive staining pattern was changed from pseudo-linear to granular just as in the case of nephrin. In 5-1-6 nephropathy podocin was co-localized with nephrin, but not in PAN nephropathy. The decrease in the expression of podocin at the mRNA level was recognized in 5-1-6 nephropathy.
In conclusion, podocin has been demonstrated to play an important role to keep the normal glomerular permoselectivity and to be a therapeutical target molecule to be examined.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (66 results)

All Other

All Publications (66 results)

  • [Publications] Morioka Y: "Podocyte injuries exacerbate mesangial proliferative glomerulonephritis"Kidney Int. 60. 2192-2204 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito Y: "Not the ED1^+ but the ED3^+ macrophage participates in the pathogenesis op irreversible glomerular changes"Acta Medica et Biologica. 49. 73-80 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ostendorf T: "Specific antagonism of PDFG prevents renal scarring in experimental glomerulonephtitis"J Am Soc Nephrol. 12. 909-918 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujigaki Y: "Sequence of events in the glomerular capillary wall at the onset of proteinuria in passive Heymann nephritis"Virchows Arch. 4388. 136-145 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe T: "Glomerular CD8^+ cells predict progression of childhood IgA nephropathy"Pediatr Nephrol. 16. 561-567 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue T: "FAT is a component of glomerular slit diaphragms"Kidney Int. 59. 1003-1012 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kasuga H: "Effects of anti-TGF-β type II receptor antibody on experimental glomerulonephritis"Kidney Int. 60. 1745-1755 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oyanagi A: "Crescent-forming mechanism in an irreversible Thy-1 model in rats"Nephron. 89. 439-447 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawachi H: "MAb 5-1-6 nephropathy and nephrin"Microsc Res Tech. 57. 236-240 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ikezumi Y: "FK506 ameliorates proteinuria and glomerular lesions induced by anti-Thy 1.1 monoclonal antibody 1-22-3"Kidney Int. 61. 1339-1350 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 清水不二雄: "糸球体濾過障壁の構造と機能"腎と透析. 50. 283-288 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 清水不二雄: "尿蛋白と尿細管間質障害"細胞. 33. 2-3 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawachi H: "Molecular structure and of the slit diaphragm : expression of nephrin in proteinuric states and in developing glomeruli"Nephrol dial Transplant. 17. 1-3 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito Y: "Fractalkine expression and the recruitment of CX_3CR^+ cells in the prolonged mesangial proliferative glomerulonephritis"Kidney Int. 61. 2044-2057 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanaka H: "Rapidly progressive, pauci-immune diffuse Crescentic glomerulonephritis in an infant"Pediatr Nephrol. 17. 730-732 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuda M: "Therapeutic effect of sulphated hyaluronic acid, a potential selctin-blocking agent, on experimental progressive mesangial proliferative glomerulonephritis"J Pathol. 198. 407-414 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 清水不二雄: "糸球体バリアの構造と機能-尿蛋白のメカニズム-"Medical Practice. 19. 448-449 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 清水不二雄: "ネフリン"医学のあゆみ. 200. 1223-1224 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 清水不二雄: "II.日本人の貢献-腎炎モデルの開発-"日本内科学会誌. 97. 1428-1431 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 清水不二雄: "腎障害と上皮細胞、内皮細胞、メサンギウム細胞"総合臨床. 51. 458-464 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawachi H: "Cloning of rat homologue of podocin : Expression in proteinuric states and in developing glomeruli"J Am Nephrol. 13. 46-56 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 清水不二雄: "糸球体腎炎の発症と治療"医歯薬出版株式会杜. 114 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 清水不二雄: "腎臓病の最新医療"先端医療技術研究所. 412 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fujigaki Y, Batsford S, Yamashita F, Yonemura K, Hishida A, Kawachi H, Shimizu F, Vogt A: "Sequence of events in glomerular capillary wall at the onset of proteinuria in passive Heymann nephritis"Virchows Archiv. 438. 136-145 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Watanabe T, Kawachi H, Ikezumi Y, Yanagihara T, Oda Y, Shimizu F.: "Glomerular CD8^+ cells predict progression of childhood IgA nephropathy"Pediatr Nephrol. 16. 561-567 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ostendorf T, Kunter U, Grone H-J, Bahlman F, Kawachi H, Shimizu F, Koch K, Janjic N, Floege J.: "Specific antagonism of PDGF prevents renal scarring in experimental glomerulonephritis"J. Am Soc Nephrol. 12. 909-918 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki K, Baba Y, Suriki H, Kawachi H, Shimizu F, Asakura H.: "Induction of Colitis and Exocrinopathy in Nude Mce Induced by Immunocompetent Cell Transfer from Murine Retrovirus-Infected Mice. H."Trends in Gastroenterology and Hepatology Springer- Verlag Tokyo. 197-200 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Bonnet F, Cooper ME, Kawachi H, Allen TJ, Boner G, Gao Z.: "Irbesartan normalizes the deficiency in glomerular nephrin expression in a model of diabetes and hypertension"Diabetologia. 44. 874-877 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue T, Yaoita E, Kurihara H, Shimizu F, Sakai T, Kobayashi T, Onshiro K, Kawachi H, Okada H, Suzuki H, Kihara I, Yamamoto T.: "FAT is a component of glomerular slit diaphragams"Kidney Int. 59. 1003-1012 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Morioka Y, Koike H, Ikezumi Y, Ito Y, Oyanagi A, Gejyo F, Shimizu F, Kawachi H.: "Podocyte injuries exacerbate mesangial proliferative glomerulonephritis"Kidney Int.. 60. 2192-2204 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oyanagi A, Orikasa M, Kawachi H, Ito Y, Koike H, Gejyo F, Shimizu F.: "Crescent-Forming Mechanism in an Irreversible Thy-1 Model in Rats"Nephron.. 89. 439-447 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kasuga H, Ito Y, Sakamoto S, Sakamoto S, Kawachi H, Shimizu F, Yuzawa, Matsuo S.: "Effects of anti-TGF-β type II receptor antibody on experimental glomerulonephritis"Kidney Int.. 60. 1745-1755 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito Y, Morioka Y, Koike H, Ikezumi Y, Kobayashi H, Gejyo F, Shimizu F, Kawachi H.: "Not the ED1^+ but the ED3^+ Macrophage Participates in the Pathogenesis of Irreversible Glomerular Changes"Acta Medica et Biologica. 49. 73-80 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamai O, Oka N, Kikuchi T, Koda Y, Soejima M, Wada Y, Fujisawa M, Tmaki K, Kawachi H, Shimizu F, Kimura H, Imaizumi T, Okuda S.: "Caveolae in mesangial cells and caveolin expression in mesangial proliferative glomerulonephritis"Kidney Int.. 59. 471-480 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawachi H, Koike H, Shimizu F.: "mAb 5-1-6 nephropathy and Nephrin"Microsc Res Tech.. 57. 236-240 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawachi H, Koike H, Shimizu F.: "Molecular structure and of the slit diaphragm : expression of nephrin in proteinuric states and in developing glomeruli"Nephrol Dial Transplant. 17. 1-3 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ikezumi Y, Kanno K, Koike H, Tomita M, Uchiyama M, Shimizu F, Kawachi H.: "FK506 ameliorates proteinuria and glomerular lesions induced by anti-Thy 1.1 monoclonal antibody 1-22-3"Kidney Int. 61. 1339-1350 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito Y, Kawachi H, Morioka Y, Nakatsue T, Koike H, Nakamura T, Gejyo F, Shimizu F.: "Fractalkine expression and the recruitment of CX_3CR1^+ cells in the prolonged mesangial proliferative glomerulonephritis"Kidney Int. 61. 2044-2057 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanaka H, Waga S, Suzuki K, Nakahata T, Kawachi H, Shimizu F, Ito E.: "Rapidly progressive, pauci-immune diffuse Crescentic glomerulonephritis in an infant"Pediatr Nephrol. 17. 730-732 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsuda M, Shikata K, Shimizu F, Suzuki Y, Miyasaka M, Kswachi H, Kawashima H, Wada J, Sugimoto H, Shikata Y, Ogawa D, Tojo S. J, Akima K, Makino H.: "Therapeutic effect of sulphated hyaluronic acid, a potential selectin-blocking agent, on experimental progressive mesangial proliferative glomerulonephritis"J Pathol. 198. 407-114 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawachi H, Koike H, Kurihara H, Sakai T, Shimizu F.: "Cloning of rat homologue of podocin : Expression in proteinuric states and in developing glomeruli"J Am Soc Nephrol. 13. 46-56 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] kawachi H: "Molecular structure and of the slit diaphragm : expression of nephrin in proteinuric states and in developing glomeruli"Nephrol dial Transplant. 17. 1-3 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ikezumi Y: "FK506 ameliorates proteinuria and glomerular lesions induced by anti-Thy 1.1 monoclonal antibody 1-22-3"Kidney Int. 61. 1339-1350 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ito Y: "Fractalkine expression and the recruitment of CX_3CR1^+ cells in the prolonged mesangial proliferative glomerulonephritis"Kidney Int. 61. 2044-2057 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tanaka H: "Rapidly progressive, pauci-immune diffuse Crescentic glomerulonephritis in an infant"Pediatr Nephrol. 17. 730-732 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Matsuda M: "Therapeutic effect sulphated hyaluronic acid, a potential selctin-blocking agent, on experimental progressive mesangial proliferative glomerulonephritis"J Pathol. 198. 407-414 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawachi H: "MAb 5-1-6 nephropathy and nephrin"Microsc Res Tech. 57. 236-240 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 清水不二雄: "糸球体バリアの構造と機能-蛋白尿のメカニズム-"Medical Practice. 19. 448-449 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 清水不二雄: "ネフリン"医学のあゆみ. 200. 1223-1224 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 清水不二雄: "II.日本人の貢献-腎炎モデルの開発-"日本内科学会誌. 91. 1428-1431 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 清水不二雄: "腎障害と上皮細胞、内皮細胞、メサンギウム細胞"総合臨床. 51. 458-464 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawachi H: "Cloning of rat homologue of podocin : Expression in proteinuric states and in developing glomeruli"J Am Nephrol. 13. 46-56 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Morioka Y: "Podocyte injuries exacerbate mesangial proliferative glomeruloncphritis"Kidney Int. 60. 2192-2204 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ito Y: "Not the ED1^+ but the ED3^+ macrophage participates in the pathogenesis of irreversible glomerular changes"Acta Medica et Biologica. 49. 73-80 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ostendorf T: "Specific antagonism of PDGF prevents renal scarring in experimental glomerulonephritis"J Am Soc Nephrol. 12. 909-918 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fujigaki Y: "Sequence of events in the glomerular capillary wall at the onset of proteinuria in passive Heymann nephrotis"Virchows Arch. 4388. 136-145 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Watanabe T: "Glomerular CD8^+ cells predict progression of childhood IgA nephropathy"Pediatr Nephrol. 16. 561-567 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Inoue T: "FAT is a component of glomerular diaphragms"Kidney Int. 59. 1003-1012 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kasuga H: "Effects of anti-TGF-β type II receptor antibody on experimental glomerulonephritis"Kidney Int. 60. 1745-1755 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Oyanagi A: "Crescent-forming mechanism in an irreversible Thy-1 model in rats"Naphron. 89. 439-447 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawauchi H: "mAb 5-1-6 nephropathy and nephrin"Microsc Res Tech. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Ikezumi Y: "FK506 ameliorates proteinuria and glomerular lesions induced by anti-Thy 1.1 monoclonal antibody 1-22-3"Kidney Int. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] 清水不二雄: "糸球体濾過過障壁の構造と機能"骨と透析. 50. 283-288 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 清水不二雄: "尿蛋白と尿細管間質障害"細胞. 33. 2-3 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 清水不二雄: "糸球体腎炎の発症と治療"医歯薬出版株式会社. 114 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 清水不二雄: "腎臓病の最新医療"先端医療技術研究所. 412 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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