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2003 Fiscal Year Final Research Report Summary

Establishment of a novel diagnostic method with a slit diaphragm functional marker, nephrin

Research Project

Project/Area Number 13557084
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Kidney internal medicine
Research InstitutionNIIGATA UNIVERSITY

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)

Co-Investigator(Kenkyū-buntansha) OKUBO Soichiro  NIIGATA UNIVERSITY, Medical and Dental Hospital, Lecturer, 医歯学総合病院, 講師 (20301856)
NARITA Ichiei  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 (20272817)
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)
OTA Yosuke  Intemational Research Corporation, Research Dept, Chief, 研究開発本部, 研究部長
Project Period (FY) 2001 – 2003
Keywordsnephrin / proteinuria / podocyte / slit diaphragm / minimal change type nephritic syndrome / membranous nephropathy / IgA nephropathy / podocin
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 whether the expression of SD components could be a diagnostic marker. In the first year of this project (2001), we analyzed the molecular nature of nephrin. In the second year (2002), we analyzed the kinetics of the expression of nephrin and other SD molecules in several experimental proteinuric states. Then, in the final year (2003), clinical studies were performed. We analyzed whether the expression of nephrin and other SD associated molecules in glomeruli of biopsy materials could be a diagnostic marker to predict the prognosis of mesangial proliferative glomerulonephritis. We also analyzed the relationship between the amount of podocyte associated molecules in urine and the disease activity of mesangial proliferative glomerulonephritis. We observed that the expression of nephrin, ZO-1 already decreased at the early stage of disease in cases with bad prognosis. We observed there was a positive causal relationship between the amount of podocalyxin, a membrane protein of podocyte, detected in urine and the disease activity of IgA nephropathy. We published these findings as manuscripts on the top journals of Nephrology field, Kidney International and Journal of American Society of Nephrology. We reported some of these results at the annual meeting of International Society of Nephrology held in Berlin in June, 2003. We also reported other results at the results obtained in this project contributed to he establishment and the spread of a novel diagnostic method with SD associated proteins.

  • Research Products

    (67 results)

All Other

All Publications (67 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
  • [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
  • [Publications] Ostendorf T: "Specific antagonism of PDFG prevents renal scarring in experimental glomerulpnephtitis"J Am Soc Nephrol. 12. 909-918 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujigaki Y: "Sequence of events in the glomerular capillary wall at the onset of proteinuria in passive Heymann nephritis"Virchows Arch. 438. 136-145 (2001)

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

    • Description
      「研究成果報告書概要(和文)」より
  • [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
  • [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
  • [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
  • [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
  • [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
  • [Publications] 河内 裕: "正常および病的状態下の糸球体濾過障壁"腎と透析. 51. 602-606 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 河内 裕: "腎糸球体上皮細胞足突起間スリット膜の構造と機能"医学のあゆみ. 198. 691-695 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [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
  • [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
  • [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
  • [Publications] Matsuda M: "Therapeutic effect of sulphated hyaluronic acid, a potential selctin-blocking agen, t, 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
  • [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)

    • Description
      「研究成果報告書概要(和文)」より
  • [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
  • [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
  • [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
  • [Publications] 河内 裕: "抗スリット膜抗体による蛋白尿"腎と透析. 53. 569-573 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 河内 裕: "遺伝子異常と蛋白尿"小児科. 43. 617-623 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawachi H: "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(和文)」より
  • [Publications] Koop K.: "Expression of podocyte-associated molecules in acquired human kidney diseases."J Am Soc Nephrol. 14. 2063-2071 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki A: "Retinoids regulate the repairing process of the podocytes in puromycin aminonucleoside-induced nephrotic rats."J Am Soc Nephrol.. 14. 981-991 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Narita I.: "Genetic polymorphism of NPHS1 modifies the clinical manifestations of Ig A nephropathy."Lab Invest.. 83. 1093-2000 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Davis BJ.: "Disparate effects of angiotensin II antagonists and calcium channel blockers on albuminuria in experimental diabetes and hypertension : potential role of nephrin."J Am Soc Nephrol.. 14. 1904-1926 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Peters H.: "Moderate alcohol intake has no impact on acute and chronic progressive anti-Thy-1 glomerulonephritis."Am J Physiol Renal Physiol.. 284. 1105-1114 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kanno K.: "Urinary sediment podocalyxin in children with glomerular diseases."Nephron Clin Pract.. 95. c91-c99 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Han GD.: "IFN-inducible protein-10 has a differential role in podocyte during Thy 1.1 elomeruloneohritis"J Am Soc Nephrol.. 14. 3111-3126 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 河内 裕: "蛋白尿発症の分子機構"腎と透析. 54. 189-193 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 河内 裕: "スリット膜関連分子群の性状"腎と透析. 55. 702-706 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 河内 裕: "蛋白尿の発症機序"小児内科. 35. 815-819 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 河内 裕: "糸球体上皮細胞の機能因子-最近明らかになった蛋白尿発症責任分子について-"診断と治療. 91. 517-522 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 河内 裕: "専門医のための腎臓医学"医学書院. 524 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Salant D.J.: "Renal injury due to antibody alone. In Immunologic renal diseases"Rave Press. 1311 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Fujigaki Y, Batsford S, Yamashita F, Yonemura K, Hishida A, Kawachi H, Simizu 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
  • [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
  • [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
  • [Publications] Suzuki K, Baba Y, Suriki H, Kawachi H, Shimizu F, Asakura H.: "Induction of Colitis and Exocrinopathy in Nude Mice 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
  • [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
  • [Publications] Inoue T, Yaoita E, Kurihara H, Shimizu F, Sakai T, Kobayashi T, Ohshiro 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
  • [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
  • [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
  • [Publications] Kasuga H, Ito Y, Sakamoto S, Sakamoto S, Kawachi H, Shimizu F, Yuzawa Y, Matauo 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
  • [Publications] Ito Y, Morioka Y, Sakamoto S, Sakamoto S, Kawachi H, 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
  • [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
  • [Publications] Kawashi 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
  • [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
  • [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 (2002)

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

    • Description
      「研究成果報告書概要(欧文)」より
  • [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
  • [Publications] Watanabe S, Suzuki K, Kawauchi Y, Yamagiwa S, Yoneyama H, Kawachi H, Okada Y, Shimizu F, Asakura H, Aoyagi Y.: "Kinetic analysis of the development of pancreatic lesions in mice infected with a murine retrovirus."Clin Immunol.. 109. 212-223 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saito A, Nagai R, Tanuma A, Hama H, Cho K, Takeda T, Yoshida Y, Toda T, Shimizu F, Horiuchi S, Gejyo F.: "Role of megalin in endocytosis of advanced glycation end products : Implications for a novel protein binding to both megalin and advanced glycation end products."J Am Soc Nephrol.. 14. 1123-1131 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] 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.: "Bioengineered implantation of megalin-expressing cells : A potential intracorporeal therapeutic model for uremic toxin protein clearance in renal failure."J Am Soc Nephrol.. 14. 2025-2032 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Narita I, goto s, Saito N, Song J, Kondo D, Omori K, Kawachi H, Shimizu F, Sakatsume M, Ueno M, Gejyo F.: "Genetic polymorphism of NPHS1 modifies the clinical manifestations of IgA nephropathy."Lab Invest.. 83. 1193-1200 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kriz W, Hahne B, Hosser H, Ostendorf T, Gaertner S, Krainzlin B, Greta N, Shimizu F, Floege J.: "Pathways to recovery and loss of nephrons in anti-Thy 1 nephritis."J Am Soc Nephrol.. 14. 1904-1926 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Peters H, Martini S, Woydt R, Ruckert M, Shimizu F, Kawachi H, Liefeldt L, Kramer S, Neumayer HH.: "Moderate alcohol intake has no impact on acute and chronic progressive anti-Thy-1 glomerulonephritis."Am J Physiol Renal Physiol.. 284. 1105-1114 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kanno K, Kawachi H, Uchida Y, Hara M, Shimizu F, Uchiyama M.: "Urinary sediment podocalyxin in Children with glomerular diseases."Nephron Clin Pract.. 95. c91-c99 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Han GD, Koike H, Nakatsue T, Suzuki K, Yoneyama H, Narumi S, Kobayashi N, Mundel P, Shimizu F, Kawachi H.: "IFN-inducible protein-10 has a differential role in podocyte during Thy 1.1 glomerulonephritis."J Am Soc Nephrol.. 14. 3111-3126 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Davis BJ, Cao Z, de Gasparo M, Kawachi H, Cooper ME, Allen TJ.: "Disparate effects of angiotensin II antagonists and calcium channel blockers on albuminuria in experimental diabetes and hypertension : potential role of nephrin."J Hypertens.. 21. 209-16 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Higuchi N, Maruyama H, Kuroda T, Kameda S, Iino N, Kawachi H, Nishikawa Y, Hanawa H, Tahara H, Miyazaki J, Gejyo F.: "Hydrodynamics-based delivery of viral interleukin-10 gene suppresses experimental crescentic glomerulonephritis in Wistar-Kyoto rats."Gene Ther.. 10. 1297-310 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Koop K, Eikmans M, Baelde HJ, Kawachi H, De Heer E, Paul LC, Brujin JA.: "Expression of podocyte-associated molecules in acquired human kidney diseases."J Am Soc Nephrol.. 14. 2063-71 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzuki A, Ito T, Imai E, Yamato M, Iwatani H, Kawachi H, Hori M.: "Retinoids regulate the repairing process of the podocytes in puromycin aminonucleoside-induced nephrotic rats."J Am Soc Nephrol.. 14. 981-91 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Orikasa M, Iwanaga T, Kawachi H, Oyanagi A, Li P, Su Q, Kobayashi H, Nakayama H, Kikuchi H, Shimizu F.: "Monoclonal antibody against rat podocyte-derived macrophagic cells ract with crescent-forming cells in an experimental model"NEPHROLOGY. 8. 217-223 (2003)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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