1995 Fiscal Year Final Research Report Summary
Elucidation of the mechanism of essential hypertension making a transgenic mice made by putative kallikrein binding protein
| Project/Area Number |
05557054
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Kidney internal medicine
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| Research Institution | Kumamoto University (1995)
Tokyo Medical and Dental University (1993-1994) |
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Principal Investigator |
TOMITA Kimio Kumamoto University, Internal Medicine, Professor, 医学部, 教授 (40114772)
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| Co-Investigator(Kenkyū-buntansha) |
INAGAKI O Yamanouchi Pharmaceutical Comp., Tsukuba Res.Institute, Researcher, 筑波研究所, 研究員
TAKENAKA T Yamanouchi Pharmaceutical Comp., Tsukuba Res.Institute, Head, 筑波研究所, 所長
TERADA Yoshio Tokyo Med.& Dent University, Internal Medicine, Assistant Professor, 医学部, 助手 (30251531)
NONOGUCHI Hiroshi Kumamoto University, Internal Medicine, Associate Professor, 医学部・附属病院, 講師 (30218341)
MARUMO Fumiaki Tokyo Med.& Dent University, Internal Medicine, Professor, 医学部, 教授 (00050443)
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| Project Period (FY) |
1993 – 1995
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| Keywords | Transgenic mice / Kallikrein / Kidney / Na / Hypertension / Nitric oxide / Glomerulus |
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| Research Abstract |
Kallikrein is a key enzyme in the processing of kininogen to release kinins, which exert diuretic and natriuretic actions. The regulation of kallikrein activities is poorly understood. Recently, Chao et al have identified a tissue specific kallikrein-binding protein that inhibits kallikrein activity, in human and rat. The gene coding for kallikrein-binding protein of rat and mouse has been subsequently cloned. It is well known that the renal kallikrein-kinin system is depressed in essential hypertension. The presence of kallikrein-binding protein in the kidney has been suggested by Western blot and Northern blot analysis. We used reverse-transcription and polymerase chain reaction to detect the precise localization of kallikrein-binding protein along the nephron using the microdissection method. In SD rats, the most abundant signals were found in inner medullary collecting duct, with small amount in outer medullary collecting duct, proximal convoluted tubule, and glomerulus. Similar distribution was found in WKY,however, in SHR,only a small amount was detected in inner medullary collecting duct. The presence of kallikrein-binding protein in terminal segment of the nephron suggests the importance of this protein in the regulation of body fluid and probably blood pressure. To explore the role of this protein in the mechanism of essential hypertension, we further tried to make transgenic mice to over-express the kallikrein-binding protein. Now we are processing the isolation of full length gene and express it to mice.
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[Publications] Yoshio Terada, Kimio Tomita, Miwako Homma, Hiroshi Nonoguchi, Tiaxin Yang, Takehisa Yamada, Yasuhito Yuasa, Edwin G.Krebs, Sei Sasaki and Fumiaki Marumo: "Sequential activation of raf-1 kinase, MAP kinase kinase, MAP kinase, and S6 kinase by hyperosmolality in renal cells." J.Biol.Chem.269. 31296-31301 (1994)
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