Identification of microRNA that regulates renal pathophysiology related to hypoxia and ER stress
| Project/Area Number |
25461207
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Inagi Reiko 東京大学, 医学部附属病院, 准教授 (50232509)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAGU Masaomi 東京大学, 医学部附属病院, 教授 (90311620)
WADA Takehiko 東京大学, 医学部附属病院, 助教 (90447409)
OHSE Takamoto 東京大学, 医学部附属病院, 臨床登録医 (10568447)
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| Research Collaborator |
JO Airi
MOTONISHI Shuta
ISHIMOTO Yu
OKADA Akira
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | エピゲノム / microRNA / 小胞体ストレス / 酸化ストレス / 虚血・再灌流 / SIRT１ / アクチン細胞骨格 / ポドサイト / 尿細管上皮細胞 / 腎臓老化 / 低酸素 / ストレスシグナル / 蛋白尿 / アクチン / コータクチン / 細胞骨格 / 糸球体腎炎 / 小胞体ストレス応答 / ATF4 / HIF / 虚血再灌流モデル |
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| Outline of Final Research Achievements |
We assessed pathophysiological significance of epigenetics, especially microRNA (miR) or SIRT1, in kidney damage.
1) We identified miR-205, whose expression was markedly decreased both under hypoxia-reoxygenation (HR) and endoplasmic reticulum (ER) stress in tubular cells, and demonstrated that miR-205 regulated stress signals induced by HR or ER stress, subsequently tubular pathological phenotypes.
2) Podocyte-specific SIRT1 deficiency showed more severe glomerular/podocyte damages than control groups under oxidative stress conditions both in vivo and in vitro. As a function of SIRT1 in podocytes, we found that SIRT1 deacetylated cortactin for maintenance of actin cytoskeleton. SIRT1 expression in podocytes were significantly upregulated under the oxidative and ER stress conditions. Collectively, SIRT1 regulates the functional state of cortactin by deacetylation, and maintains actin cytoskeleton integrity in podocytes, suggesting a novel non-epigenetic function of SIRT1 in podocytes.
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Report
(4 results)
Research Products
(89 results)
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[Journal Article] Glyoxalase I reduces glycative and oxidative stress and prevents age-related endothelial dysfunction through modulation of endothelial nitric oxide synthase phosphorylation.2014
Author(s)
Jo-Watanabe A, Ohse T, Nishimatsu H, Takahashi M, Ikeda Y, Wada T, Shirakawa J, Nagai R, Miyata T, Nagano T, Hirata Y, Inagi R, Nangaku M.
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Journal Title
Aging Cell
Volume: Epub ahead of print
Issue: 3
Pages: 519-28
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Sperm-associated antigen 4, a novel hypoxia-inducible factor 1 target, regulates eytokinesis, and its expression correlates with the prognosis of renal cell earcinoma.2013
Author(s)
Shoji K, Mimura I, Murayama T, Wada T, Kume H, Goto A, Ohse T, Tanaka T, Inagi R, van der Hoorn FA, Manabe I, Homma Y, Fukayama M, Sakurai T, Hasegawa T, Aburatani H, Kodama T, Nangaku M.
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Journal Title
American Journal of Pathology
Volume: 182
Issue: 6
Pages: 2191-2203
DOI
Related Report
Peer Reviewed
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[Presentation] CKDと炎症2015
Author(s)
稲城玲子
Organizer
第15回抗加齢学会医学会総会
Place of Presentation
福岡
Year and Date
2015-05-29 – 2015-05-31
Related Report
Invited
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