Mechanisms of regulation of ion transporters by ER stress
Project/Area Number |
15K19446
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Kidney internal medicine
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
Inoue Yuichi 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (50735834)
|
Project Period (FY) |
2015-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | 電解質 / WNKシグナル / 酸化ストレス / 塩分感受性高血圧 / 電解質異常 / 小胞体ストレス / 腎臓 |
Outline of Final Research Achievements |
Mutations in the with-no-lysine kinase 1 (WNK1), WNK4, kelch-like 3 (KLHL3), and cullin3 (CUL3) genes are known to cause the hereditary disease pseudohypoaldosteronism type II (PHAII).However, physiological in vivo roles of KLHL3 remain unclear. Therefore, here we generated KLHL3-/- mice that expressed β-galactosidase (β-Gal) under the control of the endogenous KLHL3 promoter. Immunoblots of β-Gal and LacZ staining revealed that KLHL3 was expressed in some organs, such as brain. However, the expression levels of WNK kinases were not increased in any of these organs other than the kidney. KLHL3-/- mice also showed PHAII-like phenotypes, whereas KLHL3+/- mice did not. This clearly demonstrates that the heterozygous deletion of KLHL3 was not sufficient to cause PHAII, indicating that autosomal dominant type PHAII is caused by the dominant negative effect of mutant KLHL3. We further demonstrated that the dimerization of KLHL3 can explain this dominant negative effect.
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Report
(3 results)
Research Products
(7 results)
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[Journal Article] KLHL3 Knockout Mice Reveal the Physiological Role of KLHL3 and the Pathophysiology of Pseudohypoaldosteronism Type II Caused by Mutant KLHL3.2017
Author(s)
Sasaki E, Susa K, Mori T, Isobe K, Araki Y, Inoue Y, Yoshizaki Y, Ando F, Mori Y, Mandai S, Zeniya M, Takahashi D, Nomura N, Rai T, Uchida S, Sohara E.
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Journal Title
Mol Cell Biol.
Volume: 27
Issue: 7
Pages: 1-13
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] WNK4 is an Adipogenic Factor and Its Deletion Reduces Diet-Induced Obesity in Mice.2017
Author(s)
Takahashi D, Mori T, Sohara E, Tanaka M, Chiga M, Inoue Y, Nomura N, Zeniya M, Ochi H, Takeda S, Suganami T, Rai T, Uchida S.
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Journal Title
EBioMedicine
Volume: 18
Pages: 118-27
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Comprehensive genetic testing approach for major inherited kidney diseases, using next-generation sequencing with a custom panel2017
Author(s)
Mori T, Hosomichi K, Chiga M, Mandai S, Nakaoka H, Sohara E, Okado T, Rai T, Sasaki S, Inoue I, Uchida S.
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Journal Title
Clin Exp Nephrol.
Volume: 印刷中
Issue: 1
Pages: 63-75
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Kelch-Like Protein 2 Mediates Angiotensin II-With No Lysine 3 Signaling in the Regulation of Vascular Tonus2015
Author(s)
Zeniya M, Morimoto N, Takahashi D, Mori Y, Mori T, Ando F, Araki Y, Yoshizaki Y, Inoue Y, Isobe K, Nomura N, Oi K, Nishida H, Sasaki S, Sohara E, Rai T, Uchida S
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Journal Title
J Am Soc Nephrol
Volume: 26
Issue: 9
Pages: 2129-2138
DOI
Related Report
Peer Reviewed
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[Journal Article] Impaired degradation of WNK by Akt and PKA phosphorylation of KLHL3.2015
Author(s)
Yoshizaki Y, Mori Y, Tsuzaki Y, Mori T, Nomura N, Wakabayashi M, Takahashi D, Zeniya M, Kikuchi E, Araki Y, Ando F, Isobe K, Nishida H, Ohta A, Susa K, Inoue Y, Chiga M, Rai T, Sasaki S, Uchida S, Sohara E.
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Journal Title
Biochem Biophys Res Commun.
Volume: 467
Issue: 2
Pages: 229-234
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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