Elucidation of molecular pathogenesis and development of novel therapeutic strategy of energy-sensing failure of AMPK in chronic kidney disease
Project/Area Number |
19H03672
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 53040:Nephrology-related
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Research Institution | Tokyo Medical and Dental University |
Principal Investigator |
SOHARA Eisei 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (90510355)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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Keywords | 慢性腎臓病 / エネルギー恒常性 / AMPK / AMP感受性 / 治療薬開発 / 蛋白制限食 / 臓器連関 / エネルギー代謝 / リピドミクス / エネルギー感受性 / WNK / 線維化 |
Outline of Research at the Start |
最近、我々は慢性腎臓病(CKD)においてエネルギー恒常性維持機構の中心であるAMP活性化プロテインキナーゼ(AMPK) が尿毒素やアシドーシスによってエネルギー不全(AMPの上昇)を正しく感知できなくなること、これが臓器を超えて心臓や骨格筋でも惹起され、結果として全身臓器のエネルギー不全状態を惹起することを明らかにした。本研究では、CKDにおける腎臓を含めた全身臓器のAMPKを中心としたエネルギー恒常性維持機構の破綻の詳細を明らかにし、その共通した分子機序や治療標的を明らかにする。さらに創薬スクリーニングなどによって、全く新しい概念のCKDの包括的治療法の開発を行う。
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Outline of Final Research Achievements |
AMP-activated protein kinase (AMPK) is a central kinase in energy homeostasis. AMP-induced AMPK activation is impaired in the kidneys in chronic kidney disease (CKD). In this study, we uncovered a possible role of a kinaseX, which is markedly down-regulated in CKD, in the regulation of AMP sensing by AMPK.
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Academic Significance and Societal Importance of the Research Achievements |
今回我々が発見したAMPKのAMP感知不全の分子メカニズムは、CKDにおけるエネルギー恒常性破綻の一端を解明したものであり、これを慢性腎臓病の新しい治療標的にすることにより、腎臓自身の予後を改善するとともに、臓器連関も改善し、心血管病やサルコペニアなど、慢性腎臓病の合併症の治療にも結びつくと考えられた。透析をはじめとした慢性腎臓病の患者数を減らし、さらには医療費削減にもつながる研究と考えられる意義深いものであった。
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Report
(4 results)
Research Products
(46 results)
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[Journal Article] Sodium-calcium exchanger 1 is the key molecule for urinary potassium excretion against acute hyperkalemia2020
Author(s)
Shoda W, Nomura N, Ando F, Tagashira H, Iwamoto T, Ohta A, Isobe K, Mori T, Susa K, Sohara E, Rai T, Uchida S.
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Journal Title
PLoS One.
Volume: 15(6)
Issue: 6
Pages: 0235360-0235360
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Renal TNFα activates the WNK phosphorylation cascade and contributes to salt-sensitive hypertension in chronic kidney disease2020
Author(s)
Furusho T, Sohara E, Mandai S, Kikuchi H, Takahashi N, Fujimaru T, Hashimoto H, Arai Y, Ando F, Zeniya M, Mori T, Susa K, Isobe K, Nomura N, Yamamoto K, Okado T, Rai T, Uchida S
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Journal Title
Kidney International
Volume: 97
Issue: 4
Pages: 713-727
DOI
Related Report
Peer Reviewed
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[Journal Article] HPRT-related hyperuricemia with a novel p.V35M mutation in HPRT1 presenting familial juvenile gout.2020
Author(s)
Mishima E, Mori T, Nakajima Y, Toyohara T, Kikuchi K, Oikawa Y, Matsuhashi T, Maeda Y, Suzuki T, Kudo M, Ito S, Sohara E, Uchida S, Abe T.
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Journal Title
CEN Case Rep
Volume: pub
Issue: 3
Pages: 210-214
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A familial case of pseudohypoaldosteronism type II (PHA2) with a novel mutation (D564N) in the acidic motif in WNK4.2019
Author(s)
Sakoh T, Sekine A, Mori T, Mizuno H, Kawada M, Hiramatsu R, Hasegawa E, Hayami N, Yamanouchi M, Suwabe T, Sawa N, Ubara Y, Fujimaru T, Sohara E, Shinichi U, Hoshino J, Takaichi K.
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Journal Title
Mol Genet Genomic Med
Volume: 1
Issue: 6
DOI
Related Report
Peer Reviewed
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[Presentation] TNF αは腎臓での WNK1 分解を抑 制して塩分感受性を亢進させる2019
Author(s)
古荘泰佑, 蘇原映誠, 萬代新太郎, 菊池寛昭, 高橋直宏, 藤丸拓也, 橋本博子, 新井洋平, 安藤史顕, 銭谷慕子, 森崇寧, 須佐紘一郎, 磯部清志, 野村尚弘, 岡戸丈和, 頼建光, 内田信一
Organizer
第 62 回日本腎臓学会学術総会
Related Report
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[Presentation] 腎生検にて NPHP-MCKD complex と診断された 成人症例の遺伝的背景2019
Author(s)
藤丸拓也, 蘇原映誠, 森崇寧, 萬代新太郎, 千賀宗子, 菊地寛昭, 安藤史顕, 森雄太郎, 野村 尚弘, 岡戸丈和, 頼 建光, 長田道夫, 内田信一
Organizer
第 62 回日本腎臓学会学術総会
Related Report
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[Presentation] Tubular basement membrane duplication and cell interposition are distinctive histological findings in the adult patients genetically diagnosed with NPHP-RCs2019
Author(s)
Takuya Fujimaru, Takayasu Mori, Michio Nagata, Shintaro Mandai, Motoko Chiga, Hiroaki Kikuchi, Fumiaki Ando, Yutaro Mori, Koichiro Susa, Kiyoshi Isobe, Soichiro Iimori, Naohiro Nomura, Shotaro Naito, Tomokazu Okado, Tatemitsu Rai, Shinichi Uchida, Eisei Sohara
Organizer
ASN Kidney Week
Related Report
Int'l Joint Research
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[Presentation] Renal TNF α activates WNK phosphorylation cascade and contributes to salt-sensitive hypertension in CKD2019
Author(s)
Furusho T, Mandai S, Kikuchi H, Takahashi N, Fujimaru T, Hashimoto H, Arai Y, Ando F, Mori T, Susa K, Isobe K, Nomura N, Okado T, Rai T, Yamamoto K, Uchida S, Sohara E
Organizer
ASN Kidney Week
Related Report
Int'l Joint Research
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