2016 Fiscal Year Final Research Report
Search for novel physiological function of transcriptional factor Nrf2
| Project/Area Number |
26460354
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Research Collaborator |
SEKI Shiori 東北大学, 医学部保健学科, 学生
HIRAMOTO Keiichiro 東北大学, 大学院医学系研究科, 大学院生
NAGANUMA Eriko 東北大学, 大学院医学系研究科, 技術補助員
TAKAHASHI Nobuyuki 東北大学, 大学院薬学系研究科, 准教授 (40588456)
SATO Hiroshi 東北大学, 大学院薬学系研究科, 教授 (60215829)
YAMAMOTO Masayuki 東北大学, 大学院医学系研究科, 教授 (50166823)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | Nrf2 / Keap1 / 腎性尿崩症 |
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| Outline of Final Research Achievements |
Nrf2 regulates the cellular response to oxidative/electrophilic stresses, and loss of Keap1 increases Nrf2 protein level. As Keap1-null mice die of esophageal hyperkeratosis, whole-body phenotypes of Nrf2 hyperactivation in adult animals remain to be delineated. To circumvent this problem, we deleted esophageal Nrf2 in Keap1-null mice. These mice survived until adulthood, but developed polyuria with low osmolality and bilateral hydronephrosis. This novel phenotype appears to be attributable to defects in water reabsorption caused by a reduction in the level of the AQP2 channel in the kidney. This phenotype was recapitulated by renal tubular deletion of Keap1, which generated symptoms of nephrogenic diabetes insipidus, demonstrating that Nrf2 activation in developing tubular cells causes a water reabsorption defect. Our approach to rescue mice from the lethal first hit of Keap1 ablation serves as a useful tool to study novel functions of Nrf2.
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| Free Research Field |
医化学
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