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The Role of Angiogenesis in the Progression of Tubulointerstitial Injury in the Scarred Kidney Secondary to Urinary Tract Diseases

Research Project

Project/Area Number 10470328
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionTohoku University

Principal Investigator

SAKAI Kiyohide  Tohuku University School of Medicine, Department of Urology, Research Associate, 大学院・医学系研究科, 助手 (00271908)

Co-Investigator(Kenkyū-buntansha) KONDA Ryuichiro  Tohuku University School of Medicine, Department of Urology, Associate Professor, 医学部・附属病院, 講師 (10225609)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥11,100,000 (Direct Cost: ¥11,100,000)
Fiscal Year 2000: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1999: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥5,300,000 (Direct Cost: ¥5,300,000)
Keywordskidney / renal function / fibrosis / angiogenesis / Platelet-derived endothelial cell growth factor / Interleukin-6 / Vascular endothelial growth factor / reflux nephropathy / obstructive uropathy / 血管増殖因子 / 新生血管 / 腎尿細管間質障害 / 血管増殖抑制因子
Research Abstract

In chronic inflammation, tumor growth and wound healing, hypoxia and/or inflammatory cell infiltration appear to be the common events preceding neovascularization. Tubulointerstital pathology characterized by tubular atrophy, interstitial fibrosis and mononuclear cell infiltration is primary lesion of the scarred kidneys secondary to variety of urinary tract diseases and causes local ischemia via obliteration of the postglomerular capillary network. Although angiogenesis is assumed to be upregulated in the scarred kidneys, we have little information concerning new vessel formation secondary to tubulointerstitial injury. We examined microvessel count in the scarred kidneys and elucidated that number of microvessel increased with increasing interstitial fibrosis. The expression of platelet-derived endothelial cell growth factor (PD-ECGF), one of potent stimulators for angiogenesis, increased in the tubular epithelial cells and mononuclear infiltrates located in the areas with interstitial fiborsis. A significant correlation was found between microvessel count and the degree of interstitial fibrosis or the expression of PD-ECGF.
Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen that promotes angiogenesis. We determined levels of urinary VEGF in the patients with reflux nephropathy. Urinary VEGF levels were significantly higher in the patients with severe renal scarring compared with normal controls or those with mild renal scarring. Immunohistochemical examination of VEGF showed an increased expression of this protein in the tubular epithelial cells in and adjacent to fibrotic areas where microvessel count increased. We suggest from these observations that an increase of urinary VEGF value may reflect the up-regulation of this protein.
We suggest from these observations that angiogenesis may play a critical role in the progression of tubulointerstitial injury.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] 坂井清英: "腎機能障害をきたしたVOR症例の臨床的検討-DMSA renal sccus、尿蛋白、腎組織所見による腎障害進展の予測-"日本小児泌尿器科学会雑誌. 8. 77-87 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 近田龍一郎、坂井清英: "小児逆流性腎症における尿VEGFの検討"日本小児泌尿器科学会雑誌. 8. 26-31 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 坂井清英: "新生児・乳児期に急性腎不全をきたした先天性尿路疾患の治療と予後"泌尿器外科. 13. 245-251 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 坂井清英: "尿管溜、尿道弁、尿道憩室に対する内視鏡手術"Japanese Journal of Enduurology and ESWL. 13. 68-76 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] RUICHIRO KONDA KIYOHIDE SAKAI: "Expression of Platelet-Derived Endothelial Cell Growth Factor and its Potential Role in Up-Regulation of Angiogenesis in Scarred Kidneys Secondary to Urinary Tract Diseases"American Journal of Pathology. 155. 1587-1597 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] KIYOHIDE SAKAI JUN WANG.RYUICHIRO KONDA: "CLINICAL SIGNIFICANCE OF URINARY INTERLEUKIN-6 IN CHILDREN WITH REFLUX NEPHROPATHY"THE JOURNAL OF UROLOGY. 165. 210-214 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakai K., Konda R., Ota S.et al: "A Clinical Study on Patients with Vesicoureteral Reflux Associated with Renal Dysfunction : Predictive Marker for Progression of Renal Injury."J.J.P.U.. 8. 77-87 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Konda R., Sakai K., Ota S.et al: "Vascular Endothelial Growth Factor in Children with Reflux Nephropathy."J.J.P.U.. 8. 26-31 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Konda R., Sato H., Sakai K.et al: "Expression of Platelet-Derived Endothelial Cell Growth Factor and its Potential Role in Up-Regulation of Angiogenesis in Scarred Kidneys Secondary to Urinary Tract Diseases."AJP. 155. 1587-1597 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakai K., Konda R., Ota S.et al: "Follow-up Study of Renal Function in Children Who Suffered from Acute Renal Failure Secondary to Urinary Tract Diseases in Neonatal or Infantile Period."Japanese Journal of Urological Surgery. 13. 245-251 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Konda R., Sakai K., Orikasa S.: "Congenital Renal Diseases from Clinical and Histologic Points of View."Kidney and Dialysis. 48. 175-87 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wang J., Konda R., Sakai K.et al: "Clinical Significance of Urinary Interleukin-6 in Children with Reflux Nephropathy."J.Urol.. 165. 210-214 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] JUN WANG,RYUICHIRO KONDA KIYOHIDE SAKAI: "CLINICAL SIGNIFICANCE OF URINARY INTERLEUKIN-6 IN CHILDREN WITH REFLUX NEPHROPATHY"THE JOURNAL OF UROLOGY. 165. 210-214 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 坂井清英: "新生児・乳児期に急性腎不全をきたした先天性尿路疾患の治療と予後"泌尿器外科. 13(3). 245-251 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 坂井清英: "尿管瘤・尿道弁・尿道憩室に対する内視鏡手術"Japanese Journal of Endourology and ESWL. 13(1). 68-76 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ryuichiro Konda: "Expression of Platelet-Derived Endothelial Cell Growth Foctor and its Potential Role in Upregulation of Angiogenesis in Scarred Kiclneys Secondary to Urinary Traet Diseases"American Journal of Pathdogy. vol.155No.5. 1587-1597 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 坂井 清英: "逆流防止術の長期経過観察の重要性"小児外科. 31巻4号. 419-429 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 坂井 清英: "腎機能障害をきたした VUR 症例の臨床的検討-DMSA renal scan 尿蛋白,腎組織所見による腎障害*の予測-"Japanese Journal of Pediatric Urology. vol.8, No.2. 77-87 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 近藤 龍一郎: "小児逆流性腎症における尿 VEGF の検討"Japanese Journal of Pediatric Urology. vol.8,No.2. 26-31 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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