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Development of congenital anomalies of the kidney and urinary tract (CAKUT)

Research Project

Project/Area Number 12307021
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionTokai University

Principal Investigator

ICHIKAWA Iekuni  Tokai University, School of Medicine, Professor, 医学部, 教授 (80317768)

Co-Investigator(Kenkyū-buntansha) MIYAZAKI Yoichi  Jikei University School of Medicine, Assistant Researcher, 医学部, 助手 (60266690)
MATSUSAKA Taiji  Tokai University, School of Medicine, Assistant Professor, 総合医学研究所, 講師 (50317749)
Project Period (FY) 2000 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥43,370,000 (Direct Cost: ¥36,800,000、Indirect Cost: ¥6,570,000)
Fiscal Year 2003: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2002: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2001: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Fiscal Year 2000: ¥14,900,000 (Direct Cost: ¥14,900,000)
KeywordsBMP4 / Foxc1 / CAKUT / kidney / urinary tract / development / renal hypoplasia / mouse
Research Abstract

It has been postulated that ectopia of the initial ureter budding is the first ontogenic misstep that leads to many congenital anomalies of the kidney and urinary tract (CAKUT). The ectopia can result in hypoplastic kidney, ectopia of ureterovesical orifice, urinary outflow obstruction and/or reflux. Our studies on several mutant mouse models, e.g., Bmp4 +/-, Foxc1 -/-, Agtr2 -/Y, verified that ectopic ureter budding indeed occurs prior to the formation of CAKUT. Moreover we found that BMP4, acting on the Wolffian duct and ureter epithelium, determines the budding site of the ureter by locally antagonizing ubiquitous inductive signal(s) from the metanephric mesenchyme. However, analyses of Foxc1 -/-revealed that, whereas ectopic ureter can result in hypoplastic kidney and ureter morphological abnormality, it cannot cause formation of multicystic dysplastic kidney, a well-known renal abnormality seen in human CAKUT. Often, the genes involved in navigating the site of ureteral budding also regulate later ontogenic processes of the kidney and other urinary tract system. For example, BMP4 has multiple biological' functions during kidney and urinary tract formation as follows. In addition to determining budding site of the ureter, BMP4 (1) stimulates elongation of the budding ureter, 2) promotes growth of the metanephric mesenchyme by inhibiting apoptosis, and 3) has a role on the formation of glomerular tuft during glomerulogenesis. Thus, these additional functions of the genes underlie the wide spectrum of CAKUT, as the genes are expressed at multiple sites at multiple ontogenic stages, and regulate the morphogenesis of the many portions Qf the excretory system through their distinctive cellular functions.

Report

(5 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (48 results)

All Other

All Publications (48 results)

  • [Publications] Miyazaki Y, Oshima K, Fogo A, Hogan B.L.M., Ichikawa I: "Bone morphogenetic protein 4 regulates the budding site and elongastion of the mouse ureter"The Journal of Clinical Investigation. 105(7). 863-873 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujinaka H, Miyazaki Y, Matsusaka T, Yoshida H, Fogo A, Inagami T, Ichikawa I: "Salutary role for angiotensin in partial urinary tract obstruction"Kidney International. 58(5). 2018-2027 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyazaki Y, Ichikawa I: "Role of the angiotensin receptor in the development of the mammalian kidney and urinary tract"Comparative Biochemistry Physiology. Part A, Molecular and Intergrative Physiology. 128(1). 89-97 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Pope JC, Brock JW, Adams MC, Miyazaki Y, Stephens FD, Ichikawa I: "Congenital anomalies of the kidney and urinary tract-role of the loss of function mutation in the pluripotent angiotensin type 2 receptor gene"Journal of Urology. 165(1). 196-202 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyazaki Y, Ichikawa I: "Nephrotoxicity angiotensin inhibition during the perinatal period"Experimental Nephrology. 9(1). 10-13 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Oshima K, Miyazaki Y, Brock JW 3rd, Adams MC, Ichikawa I: "Angiotensin type II receptor expression and ureteral budding"The Journal of Urology. 166(5). 1848-1852 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichikawa I, Miyazaki Y: "Guarding the kidney architecture : newly recognized physiological role of angiotensin"Contributions to Nephrology. 135. 111-122 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takaya J, Matsusaka T, Katori H, Tamura M, Miyazaki Y, Homma T, Ichikawa I: "In situ demonstration of angiotensin-dependent and independent pathways for hyperaldosteronism during chronic extracellular fluid volume depletion"Molecular Endocrinology. 15(12). 2229-2235 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsusaka T, Miyazaki Y, Ichikawa I: "The Renin Angiotensin system and Kidney development"Annual Review of Physiology. 64. 551-561 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishida M, Fujinaka H, Matsusaka T, Price J, Kon V, Fogo AB, Davidson JM, Linton MF, Fazio S, Homma T, Yoshida H, Ichikawa I: "Absence of angiotensin II type 1 receptor in bone marrow-derived cell is detrimenta in the evolution of renal fibrosis"The Journal of Clinical Investigation. 110(12). 1859-1868 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kuwayama F, Miyazaki Y, Ichikawa I: "Embryogenesis for the congenital anomalies of the kidney and the urinary tract"Nephrol.Dial.Transplant.. 17 Suppl9. 45-47 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichikawa I, Kuwayama F, Pope JC 4^<th>, Stephens FD, Miyazaki Y: "Paradigm shift from classic anatomic theories to contemporary cell biological views of CAKUT"Kidney International. 61(3). 889-898 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyazaki Y, Oshima K, Fogo A, Ichikawa I: "Evidence that bone morphogenetic protein 4 has multiple biological functions during kidney and urinary tract development"Kidney International. 63(3). 835-844 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyazaki Y, Ichikawa I: "Ontogeny of congenital anomalies of the kidney and urinary tract, CAKUT"Pediatr Int.. 45(5). 598-604 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakano T, Niimura F, Hohenfellner K, Miyakita E, Ichikawa I: "Screening for mutations in BMP4 and FOXC1 genes in congenital anomalies of the kidney and urinary tract in humans"The Tokai Journal of Experimental and Clinical Medicine. In press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Xin J, Homma T, Matsusaka T, Ma J, Isaka Y, Imai E, Ichikawa I: "Suppression of cyclosporine A nephrotoxicity in vivo by transforming growth factor-β receptor-IgG chimeric protein"Transplantation. In press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyazaki Y, Oshima K, Fogo A, Hogan B.L.M., Ichikawa I: "Bone morphogenetic protein 4 regulates the budding site and elongastion of the mouse ureter"The Journal of Clinical Investigation. 105(7). 863-873 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fujinaka H, Miyazaki Y, Matsusaka T, Yoshida H, Fogo A, Inagami T, Ichikawa I: "Salutary role for angiotensin in partial urinary tract obstruction"Kidney International. 58(5). 2018-2028 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyazaki Y, Ichikawa I: "Role of the angiotensin receptor in the development of the mammalian kidney and urinary tract"Comparative Biochemistry Physiology. Molecular and Intergrative Physiology. 128(1). 89-87 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Pope JC, Brock JW, Adams MC, Miyazaki Y, Stephens FD, Ichikawa I: "Congenital anomalies of the kidney and urinary tract-role of the loss of function mutation in the pluripotent angiotensin type 2 receptor gene"Journal of Urology. 165(1). 196-202 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyazaki Y, Ichikawa I: "Nephrotoxicity angiotensin inhibition during the perinatal period"Experimental Nephrology. 9(1). 10-13 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Oshima K, Miyazaki Y, Brock JW 3rd, Adams MC, Ichikawa I: "Angiotensin type II receptor expression and ureteral budding"Journal of Urology. 166(5). 1848-1852 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Ichikawa I, Miyazaki Y: "Guarding the kidney architecture : newly recognized physiological role of angiotensin"Contributions to Nephrology. 135. 111-122 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takaya J, Matsusaka T, Katori H, Tamura M, Miyazaki Y, Homma T, Ichikawa I: "In situ demonstration of angiotensin-dependent and independent pathways for hyperaldosteronism during chronic extracellular fluid volume depletion"Molecular Endocrinology. 15(12). 2229-2235 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Matsusaka T, Miyazaki Y, Ichikawa I: "The Renin Angiotensin system and Kidney development"Annual Review of Physiology. 64. 551-561 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nishida M, Fujinaka H, Matsusaka T, Price J, Kon V, Fogo AB, Davidson JM, Linton MF, Fazio S, Homma T, Yoshida H, Ichikawa I: "Absence of angiotensin II type 1, receptor in bone marrow-derived cell is detrimenta in the evolution of renal fibrosis"The Journal of Clinical Investigation. 110(12). 1859-1868 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kuwayama F, Miyazaki Y, Ichikawa I: "Embryogenesis for the congenital anomalies of the kidney and the urinary tract"Nephrol. Dial. Transplant.. 17Suppl 9. 45-47 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Pope JC 4^<th>, Stephens FD, Miyazaki Y: "Paradigm shift from classic anatomic theories to contemporary cell biological views of CAKUT"Kidney International. 61(3). 889-898 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyazaki Y, Oshima K, Fogo A, Ichikawa I: "Evidence that bone morphogenetic protein 4 has multiple biological functions during kidney and urinary tract development"Kidney International. 63(3). 835-844 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyazaki Y, Ichikawa I: "Ontogeny of congenital anomalies of the kidney and urinary tract, CAKUT"Pediatrics International. 45(5). 598-604 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakano T, Niimura F, Hohenfeliner K, Miyakita E, Ichikawa I: "Screening for mutations in BMP4 and FOXC1 genes in congenital anomalies of the kidney and urinary tract in humans"The Tokai Journal Medicine. (In press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Xin J, Homma T, Matsusaka T, Ma J, Isaka Y, Imai E, Ichikawa I: "Suppression of cyclosporine A nephrotoxicity in vivo by transforming growth factor-β receptor-IgG chimeric protein"Transplantation. (In press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Miyazaki Y, Ichikawa I: "Ontogeny of congenital anomalies of the kidney and urinary tract, CAKUT"Pediatr Int.. 45(5). 598-604 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Naoko T, Niimura F, Hohenfellner K, Miyakita E, Ichikawa I: "Screening for mutations in BMP4 and FOXC1 genes in congenital anomalies of the kidney and urinary tract in humans"The Tokai Journal of Experimental and Clinical Medicine. (In press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Xin J, Homma T, Matsusaka T, Ma J, Isaka Y, Imai E, Ichikawa I: "Suppression of cyclosporine A nephrotoxicity in vivo by transforming growth factor-β receptor-IgG chimeric protein"Transplantation. (In press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Nishida M, Fujinaka H, Matsusaka T, Price J, Kon V, Fogo AB, Davidson JM, Linton MF, Fazio S, Homma T, Yoshida H, Ichikawa I: "Absence of angiotensin II type 1 receptor in bone marrow-derived cells is detrimental in the evolution of renal fibrosis"The Journal of Clinical Investigation. 110(2). 1859-1868 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kuwayama F, Miyazaki Y, Ichikawa I: "Embryogenesis of the congenital anomalies of the kidney and the urinary tract"Nephrol. Dial. Transplant.. 17 Suppl9. 45-47 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ichikawa I, Kuwayama F, Pope JC 4^<th>, Stephens FD, Miyazaki Y: "Paradigm shift from classic anatomic theories to contemporary cell biological views of CAKUT"Kidney International. 61(3). 551-561 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Miyazaki Y, Keisuke O, Fogo A, Ichikawa I: "Evidence that bone morphogenetic protein 4 has multiple biological functions during kidney and urinary tract development"Kidney International. 63(in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Oshima K, Miyazaki Y, Brock JW 3rd, Adams MC, Ichikawa I, Pope JC 4th: "Angiotensin type II receptor expression and ureteral budding"The Journal of Urology. 166(5). 1848-52 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ichikawa I, Miyazaki Y: "Guarding the kidney architecture:newly recognized physiological role of angiotensin"Contributions to Nephrology. 135. 111-22 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takaya J, Matsusaka T, Katori H, Tamura M, Miyazaki Y, Homma T, Ichikawa I: "In situ demonstration of angiotensin-dependent and independent pathways for hyperaldosteronism during chronic extracellular fluid volume depletion"Molecular Endocrinology. 15(12). 2229-35 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsusaka T, Miyazaki Y, Ichikawa I: "The Renin Angiotensin system and kidney development"Annual Review of Physiology. 64. 551-61 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Miyazaki Y,Oshima K,Fogo A,Hogan B.L.M,Ichikawa I: "Bone morphogenetic protein 4 regulates the budding site and elongation of the mouse ureter"The Journal of Clinical Investigation. Apr.105(7). 863-873 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujinaka H,Miyazaki Y,Matsusaka T,Yoshida H,Fogo A,Inagami T,Ichikawa I: "Salutary role for angiotensin in partial urinary tract obstruction"Kidney International. Nov.58(5). 2018-27 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyazaki Y,Ichikawa I: "Role of the angiotensin receptor in the development of the mammalian kidney and urinary tract."Comparative Biochemistry Physiology. Part A, Molecular and Integrative Physiology. Jan;128(1). 89-97 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Pope JC,Brock JW,Adams MC,Miyazaki Y,Stephens FD,Ichikawa I: "Congenital anomalies of the kidney and urinary tract-role of the loss of function mutation in the pluripotent angiotensin type 2 receptor gene"Journal of Urology. Jan.165(1). 196-202 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyazaki Y,Ichikawa I: "Nephrotoxicity of angiotensin inhibition during the perinatal period"Experimental Nephrology. 9(1). 10-3 (2001)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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