Therapeutic intervention of CKD targeting cellular oxygen sensors
Project/Area Number |
17K09688
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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 |
Research Field |
Kidney internal medicine
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Research Institution | The University of Tokyo |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
川上 貴久 杏林大学, 医学部, 学内講師 (10722093)
稲城 玲子 東京大学, 医学部附属病院, 特任教授 (50232509)
南学 正臣 東京大学, 医学部附属病院, 教授 (90311620)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 低酸素 / プロリン水酸化酵素 / 慢性腎臓病 / HIF / PHD阻害薬 / 肥満関連腎症 / 糖尿病性腎臓病 |
Outline of Final Research Achievements |
In this study, we investigated the impact of prolyl hydroxylase (PHD) inhibition in CKD progression. In BTBR/obob type 2 diabetes mice and obese mice fed with high fat diet, inhibition of PHD using PHD inhibitors significantly reduced albuminuria, which was associated with reduced glomerular infiltration of macrophages and amelioration in glomerulosclerosis. Inhibition of the cellular oxygen sensor, PHD, may be a novel therapeutic target in glomerular injury associated with type 2 diabetes and obesity.
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Academic Significance and Societal Importance of the Research Achievements |
慢性腎臓病(CKD)を有する人口は1000万人を超えるが、治療介入の手段は限られている。近年、低酸素生物学の進歩により、新規腎性貧血治療薬としてプロリン水酸化酵素阻害薬(PHD阻害薬)が開発され、臨床応用が開始された。本薬剤は細胞内の低酸素センサーを阻害し、低酸素応答を強化することから低酸素障害を共通背景に有する慢性腎臓病に対して保護的に作用する可能性が考えられ、本研究では同仮設を検証した。PHD阻害によって糸球体硬化とアルブミン尿の改善が認められ、CKDの進行を抑制できる可能性が示された。
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Report
(4 results)
Research Products
(58 results)
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[Journal Article] Conditions, pathogenesis, and progression of diabetic kidney disease and early decliner in Japan2020
Author(s)
Yoshida Y, Kashiwabara K, Hirakawa Y, Tanaka T, Noso S, Ikegami H, Ohsugi M, Ueki K, Mita T, Watada H, Koya D, Mise K, Wada J, Shimizu M, Wada T, Ito Y, Narita I, Kashihara N, Nangaku M, Matsuyama Y
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Journal Title
BMJ Open Diabetes Research & Care
Volume: 8
Issue: 1
Pages: 1-8
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Mitochondrial damage causes inflammation via cGAS-STING signaling in acute kidney injury2019
Author(s)
Hiroshi Maekawa, Tsuyoshi Inoue, haruki Ouchi, Tzu-Ming Jao, Reiko Inoue, Hiroshi Nishi, Rie Fujii, Fumiyoshi Ishidate, Tetsuhiro Tanaka, Yosuke Tanaka, Nobutaka Hirokawa, Masaomi Nangaku, Reiko Inagi
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Journal Title
Cell Reports
Volume: 29
Issue: 5
Pages: 1261-1273
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Global kidney health 2017 and beyond: a roadmap for closing gaps in care, research, and policy.2017
Author(s)
Levin A, Tonelli M, Bonventre J, Coresh J, Donner JA, Fogo AB, Fox CS, Gansevoort RT, Heerspink HJL, Jardine M, Kasiske B, Köttgen A, Kretzler M, Levey AS, Luyckx VA, Mehta R, Moe O, Obrador G, Pannu N, Parikh CR, Perkovic V, Pollock C, Stenvinkel P, Tuttle KR, Wheeler DC, Eckardt KU et al.
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Journal Title
Lancet.
Volume: 390
Issue: 10105
Pages: 1888-1917
DOI
Related Report
Peer Reviewed
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