| Project/Area Number |
06404041
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
MARUMO Fumiaki Tokyo Medical and Dental University, Professor, 医学部, 教授 (00050443)
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| 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)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥40,800,000 (Direct Cost: ¥40,800,000)
Fiscal Year 1996: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 1995: ¥16,800,000 (Direct Cost: ¥16,800,000)
Fiscal Year 1994: ¥19,700,000 (Direct Cost: ¥19,700,000)
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| Keywords | kidney / Transportation / Water channel / chloride channel / 集合管 / 輸送体 / クロライドキャネル / 水チャネル / バゾプレゥシン / ADH / 浮腫 / 脱水 / 腎尿細管 |
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| 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.
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