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1996 Fiscal Year Final Research Report Summary

Urine concentrating mechanisms examined by molecular biology based techniques

Research Project

Project/Area Number 06404041
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionTokyo Medical and Dental University

Principal Investigator

MARUMO Fumiaki  Tokyo Medical and Dental University, Professor, 医学部, 教授 (00050443)

Co-Investigator(Kenkyū-buntansha) TERADA Yoshio  Tokyo Medical and Dental University, Instructor, 医学部, 助手 (30251531)
KUWAHARA Michio  Tokyo Medical and Dental University, Assistant Professor, 医学部, 講師 (60221230)
SASAKI Sei  Tokyo Medical and Dental University, Associate Professor, 医学部, 助教授 (60170677)
Project Period (FY) 1994 – 1996
Keywordskidney / Transportation / Water channel / chloride channel / 集合管 / 輸送体
Research Abstract

In this research, we intended to clarify three aspects of the mechanisms underlying kidney urinary concentrating ability.
1) Cloning of transport proteins related to kidney urinary concentrating ability and examinationof their structure and function relationships. As new trasporters, we have cloned AQP3, AQP6, ClC-K2, ClC-3, and ClC-5. AQP3 is the basolateral type water channel of kidney collecting duct and it permeates small solutes such as glycerol. AQP6 also belongs to the same subfaily as AQP3, and it functional characters are similar to AQP3. ClC-5 has an unique character of strong outward rectification and its mRNA distributes in many tissues.
2) Idnetification of the signaling mechanisms controlling urinary concentrating ability. We observed the upregulation of mRNA of AQP2 and AQP3 by dehydration. The mechanisms for this regulation was identifyed by isolation of genomic sequences of the 5'region of the both genes. We also identified that A-kinse plays critical roles in the regulation of AQP2. Similar studies are under way for ClC-K1 and ClC-K2.
3) Application of basic research information ot clinical medicine. Research results obtained in this project have many implication to clinical field. Regulation of AQP2 was examined in many experimental models of water balance disorders. Urinary measurement of AQP2 has been shown to be of clinical importance in diagnosis of water balance disorders. Also immunohistochemical study using antibodies against AQPs differentiated the origin of renal carcinoma.

  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Bai L,Fushimi K,Sasaki S,Marumo F: "Structure of aquaporin-2 vasopressin water channel" J. Biol. Chem.271. 5171-5176 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tamura H,Schild L,Enomoto NMatsui N,Marumo F,Rossier BC Sasaki S: "Liddle disease caused by a missense mutation of b-subnuit of the epithelial sodium channel gene." J. Clin. Invest.97. 1780-1784 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hayashi M,Sasaki S,Tsuganezawa H Monkawa T,Kitajima W,Konishi K,Fushimi K,Marumo F,Saruta T: "Role of vasopressin V2 receptor in acute regulation of aquaporin-2." Kidney Blood Press. 19. 32-37 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Saito-Ohara F,Uchida S,Takeuchi Y,Sasaki S,Hayashi A,Marumo F,Ikeuchi T: "Assignment of the genes encoding the human chloride channels. CLCNKA and CLCNKB,to lp36 and CLCN3 to 4q32-q33 by in situ hybridization" GENOMICS. 36. 372-374 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Furuno M,Uchida S,Marumo F,Sasaki S: "Repressive regulation of the aquqporin-2 gene." Am. J. Physiol.271. F854-F860 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Uchida S,Sasaki S,Marumo F,: "Chloride transport across kidney epithelia through CIC chloride channels" Jpn. J. Nephrol.38. 285-289 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Uchida S,Sasaki S,Nitta K,Uchida K,Horita S,Nihei H,Marumo F: "Localization and functional characterization of rat kidneyspecific chloride channel,CIC-Kl" J. Clin. Invest.95. 104-113 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Inase N,Fushimi K,Ishibashi K,Uchida S,Ichioka M,Sasaki S,Marumo F: "Isolation of human aquaporin 3 gene." J. Biol. Chem.270. 17913-17916 (1995)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Bai L,Fushimi K,Sasaki S,Marumo F: "Structure of aquqporin-2 vasopressin water channel." J.Biol.Chem.271. 5171-5176 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tamura H,Schild L,Enomoto N,Matsui N,Marumo F,Rossier BC,Sasaki S: "Liddle disease caused by a missense mutation of b-subunit of the epithelial sodium channel gene." J.Clin.Invest.97. 1780-1784 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sakamoto H,Kawasaki M,Uchida S,Sasaki S,Marumo F: "Identification of a new outwardly retified Cl channel that belongs to a subfamily of the ClC Cl channels." J.Biol.Chem.271. 10210-10216

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saito-Ohara F,Uchida S,Takeuchi Y,Sasaki S,Hayashi A,Marumo F,Ikeuchi T: "Assignment of the genes encoding the human chloride channels, CLCNKA and CLCNKB,to 1p36 and CLCN3 to 4q32-q33 by in situ hybridization" Genomics. 36. 372-374 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hyayashi M,Sasaki S,Tsuganezawa H,Monkawa T,Kitajima W,Konishi K,Fushimi K,Marumo F,Saruta T: "Role of vasopressin V2 receptor in acute regulation of aquaporin-2." Kidney Blood Press.Res.19. 32-37 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Furuno M,Uchida S,Marumo F,Sasaki S: "Repressive regulation of the aquqporin-2 gene." Am.J.Physiol.271. F854-F860 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Uchida S,Sasaki S,Marumo F: "Chloride transport across kidney epithela through ClC chloride channels." Jpn.J.Nephrol.38. 285-289 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Terada Y,Yamada T,Sasaki S,Marumo F: "Overexpression of cell cycle inhibitors (p16NK4 and p21 cip1) and cyclin D1 using adenovirus regulates proliferation of rat mesangial cells" J.Am.Soc.Nephrol.8. 51-60 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Saito T,Ishikawa S,Sasaki S,Fujita N,Fushimi K,Okada K,Takeuchi K,Sakamoto A,Ookawara S,Kaneko T,Marumo F,Saito T: "Alteration in water channel AQP-2 by removal of AVP stimulation in collecting duct cells of dehydrated rats." Am.J.Physiol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yamamoto T,Sasaki S,Fushimi K,Ishibashi K,Yaoita E,Fujinaka H,Marumo F, Kihara I: "Expression of AQP family in rat kidneys during the development and maturation." Am.J.Physiol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishibashi K,Sasaki S,Fushimi K,Yamamoto T,Kuwahara M, Marumo F: "Immunolocalization and effect of dehydration on AQP3." Am.J.Physiol.(in press).

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

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Published: 1999-03-09  

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