Relationship between WNK kinase and hypertension in polycystic kidney disease
| Project/Area Number |
20890062
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| Research Category |
Grant-in-Aid for Young Scientists (Start-up)
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| Allocation Type | Single-year Grants |
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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 |
SOHARA Eisei Tokyo Medical and Dental University, 医歯学総合研究科, 助教 (90510355)
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| Project Period (FY) |
2008 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥3,302,000 (Direct Cost: ¥2,540,000、Indirect Cost: ¥762,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,742,000 (Direct Cost: ¥1,340,000、Indirect Cost: ¥402,000)
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| Keywords | 塩分感受性高血圧 / インスリン / NaCl共輸送体 / WNKキナーゼ / 高血圧 / 多発性嚢胞腎 |
|---|
| Research Abstract |
The metabolic syndrome causes hyperinsulinemia and enhances salt-sensitive hypertension. However, the mechanisms responsible for the greater salt-sensitivity in hyperinsulinemic patients are still unknown. Pseudohypoaldosteronism type II (PHAII) is an autosomal dominant disease characterized by salt-sensitive hypertension due to increased sodium reabsorption in the kidney through activation of the WNK kinase-OSR1/SPAK kinase-NaCl cotransporter (NCC) phosphorylation cascade, which we recently discovered. We found that a PHAII-causing mutant WNK4 (WNK4 R1185C) abnormally increased phosphorylation of WNK4 at serine 1190, which resulted in activation of the downstream OSR1/SPAK-NCC phosphorylation cascade. Furthermore, we clarified that insulin is a powerful stimulator for WNK4 1190S phosphorylation, thereby activating the WNK-OSR1/SPAK-NCC cascade in vitro and in vivo. Thus, our results clearly show that a hyperinsulinemic condition causes salt-sensitive hypertension by the same mechanism as identified in PHAII. However, we could not find the significant relationship between PKD and WNK kinase.
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Report
(3 results)
Research Products
(26 results)
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[Journal Article] Calcium-alkali syndrome-like symptoms manifested by daily alphacalcidol and thiazide2010
Author(s)
Satoh F, Okado T, Iwamoto M, Akita W, Wakabayashi M, Ohta A, Sohara E, Noda Y, Rai T, Uchida S, Sasaki S.
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Journal Title
Intern Med. 49(9)
Pages: 837-40
NAID
Related Report
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[Journal Article] Pancreas-specific aquaporin 12 null mice showed increased susceptibility to caerulein-induced acute pancreatitis2009
Author(s)
Ohta E, Itoh T, Nemoto T, Kumagai J, Ko SB, Ishibashi K, Ohno M, Uchida K, Ohta A, Sohara E, Uchida S, Sasaki S, Rai T.
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Journal Title
Am J Physiol Cell Physiol. 297(6)
Related Report
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[Journal Article] Pancreas specific aquaporin 12 null mice showed increased susceptibility to caerulein-induced acute pancreatitis.2009
Author(s)
Ohta E, Itoh T, Nemoto T, Kumagai J, Ko SB, Ishibashi K, Ohno M, Uchida K, Ohta A, Sohara E, Uchida S, Sasaki S, Rai T.
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Journal Title
Am J Physiol Cell Physiol. 297
Related Report
Peer Reviewed
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