2022 Fiscal Year Final Research Report
Sodium transporters in renal proximal tubules: a novel therapeutic target of cardio-renal syndrome
Project/Area Number |
20K08640
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53040:Nephrology-related
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Research Institution | Kyoto Prefectural University of Medicine |
Principal Investigator |
Kusaba Tetsuro 京都府立医科大学, 医学(系)研究科(研究院), 助教 (60367365)
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Co-Investigator(Kenkyū-buntansha) |
的場 聖明 京都府立医科大学, 医学(系)研究科(研究院), 教授 (10305576)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | うっ血性心不全 / 近位尿細管 / Naチャネル |
Outline of Final Research Achievements |
Given the success of SGLT2 inhibitors for improving the prognosis of kidney disease and heart failure (HF) patients, the sodium transporters in proximal tubules are attractive therapeutic targets. In this study, we focused on NaPi2a, a renal tubular sodium channel, as a novel candidate therapeutic target for (HF), and investigated the cardioprotective effect of its functional suppression in HF mouse model. In the TAC model, a model of pressure-overload HF, left ventricular ejection fraction was maintained, and an increase in HF markers such as ANP and BNP was suppressed in NaPi2a-KO mice. In contrast, NaPi2a suppression exhibited the no cardioprotective effects in the 5/6 nephrectomy model, a model of uremic cardiomyopathy. The mechanisms of cardioprotective effect of NaPi2a suppression in pressure-overload HF might be primarily due to a fluid volume reduction effect mediated by Na excretion, rather than due to a decrease in FGF23 associated with phosphorus excretion.
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Free Research Field |
腎臓病学
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Academic Significance and Societal Importance of the Research Achievements |
高齢化社会を迎え、心不全、腎不全の患者数は増加しており、新たな治療補の開発が望まれています。そこで今回我々は、近位尿細管で発現し、ナトリウムとリンを再吸収する輸送体であるNaPi2aに注目し、その機能を抑制することにより心不全が改善するかを検討しました。心不全を合併したNaPi2aの機能喪失マウスでは、通常心不全マウスに比し体外へのナトリウムの排泄が促され、結果としてマウス心不全モデルの心機能を保持できることが示されました。このことから、今後は同分子の抑制薬は新規の心不全治療薬になる可能性があります。
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