| Project/Area Number |
17K16095
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Kidney internal medicine
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ミネラルコルチコイド受容体（MR） / 高血圧 / 食塩感受性 |
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| Outline of Final Research Achievements |
Intestinal epithelial cells-specific mineralocorticoid receptor knockout (IEC-MR KO) mice showed significantly increased fecal Na excretion and accompanied reduced urinary Na excretion. In contrast, increased urinary Na excretion in renal tubular cells-specific MR knockout mice was compensated by suppression of fecal Na excretion. These results show that both intestinal MR and renal MR play essential roles in Na homeostasis and have mutual complementary relationship. In addition, compared to normal diet, high fat diet elevated blood pressure and increased body weight, urinary albumin and the expression of MR target genes in control mice. These changes tended to be attenuated in IEC-MR KO mice. This study suggests that intestinal MR is not only associated with Na homeostasis but also has a potential to affect the metabolic function and organ disorders.
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| Academic Significance and Societal Importance of the Research Achievements |
MR拮抗薬による心不全患者の生命予後改善効果が複数の大規模臨床研究で示されたことで、近年は様々な臓器における組織特異的MR機能の解析が行われている。本研究では腸MR-KOマウスを用いた機能解析により、これまでに未解明であった腸MRの多面的な機能を見出しつつある。この腸MRと相補的な関係にある腎MR機能との対比を通して、腸MR・腎MRの病態的役割を解明し、MRを介した代謝障害・臓器障害に対する新たな治療的アプローチの開発につながるものと期待される。
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