| Project/Area Number |
18K15995
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 53040:Nephrology-related
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
Nomura Naohiro 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (50735800)
|
|---|
| Project Period (FY) |
2018-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Keywords | 血圧 / 電解質 / バーター症候群 / ギッテルマン 症候群 / カルシニューリン阻害剤 / カリウム排泄機構 / ナトリウム輸送体 / カルシニューリン / カリウム / 高血圧 |
|---|
| Outline of Final Research Achievements |
High potassium (K) intake decreases hypertension and associated lower mortality. On the other hand, hyperkalemia causes sudden death with fatal cardiac arrhythmia and is also related to higher mortality.
Renal sodium (Na)-chloride (Cl) cotransporter (NCC), expressed in the distal convoluted tubule, is a key molecule in regulating urinary K excretion. K intake affects the activity of the NCC, which is related to salt-sensitive hypertension. NCC is known to be regulated by WNK-SPAK signal cascade. We discovered that the suppression of NCC by K loading was regulated by another mechanism. We found that calcium signal through sodium-calcium exchanger (NCX) stimulates calcineurin, which dephosphorylates NCC. This finding could lead to novel treatment against Gitelman syndrome, which is caused by loss of function of NCC.
|
| Academic Significance and Societal Importance of the Research Achievements |
ナトリウムクロライド共輸送体は、腎臓においてナトリウムやカリウムのバランスをとるために主要な役割を担っており、この輸送体のメカニズムを明らかとすることは、血圧管理・体内の水分・電解質バランス調整に役立つと考えられる。
また、ナトリウム輸送体の機能障害が原因であるギッテルマン 症候群やバーター症候群の発症にも関わっており、これらの疾患の治療につながる可能性がある。
|
