Mechanisms of moyamoya-susceptible gene expression by interferon and the establishment of preventive medicine for cerebrovascular disease
Project/Area Number |
26460801
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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 |
Hygiene and public health
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Research Institution | St. Marianna University School of Medicine (2015-2016) Kyoto University (2014) |
Principal Investigator |
Hitomi Toshiaki 聖マリアンナ医科大学, 医学部, 准教授 (90405275)
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Co-Investigator(Kenkyū-buntansha) |
小泉 昭夫 京都大学, 医学研究科, 教授 (50124574)
小林 果 京都大学, 医学研究科, 特定講師 (70542091)
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 予防医学 / もやもや病 / mysterin(RNF213) / インターフェロン / 脳血管疾患 / 血管内皮細胞 / iPS細胞 / 感染症 / Mysterin(RNF213) / R4810K / Mysterin / RNF213 / 疾患iPS細胞 |
Outline of Final Research Achievements |
Mysterin (RNF213) is a susceptibility gene for moyamoya disease (MMD) and its coding variant, p.R4810K, is a common founder variant in East Asian countries. Several angiogenic and anti-angiogenic factors [including interferons (IFNs), IFN-β and IFN-γ] induced transcriptional expression of mysterin in human umbilical vein endothelial cells (HUVECs). In HUVECs, upregulation of mysterin by IFN-β is mediated by a STAT1-binding site on the mysterin gene promoter. The anti-angiogenic activities of IFN-β are partially rescued by siRNA for STAT1, and completely rescued by siRNA for mysterin. Treatment with IFN-β induced mysterin mRNA and decreased angiogenesis in induced pluripotent stem cells-derived vascular endothelial cells (iPSECs) derived from control subjects and patients with MMD. Our data suggest that mysterin mediates the IFN-β anti-angiogenic signaling pathway; MMD may impair angiogenesis in patients with infectious or autoimmune disease.
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Infantile pain episodes associated with novel Nav1.9 mutations in familial episodic pain syndrome in Japanese families2016
Author(s)
Hiroko Okuda, Atsuko Noguchi, Hatasu Kobayashi, Daiki Kondo, Kouji H.Harada, Shohab Youssefian, Hirotomo Shioi, Risako kabata, Yuki Domon,Kazufumi Kubota, Yutaka Kitano, Yasunori Takayama, Toshiaki Hitomi,Kousaku Ohno, Yoshiaki Saito, Takeshi Asano, Makoto Tominaga, Tsutomu Takahashi, and Akio Koizumi.
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Journal Title
PLOS ONE
Volume: 11
Issue: 5
Pages: e0154827-e0154827
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] PTP1B controls non-mitochondrial oxygen consumption by regulating RNF213 to promote tumour survival during hypoxia.2016
Author(s)
Banh RS, Iorio C, Marcotte R, Xu Y, Cojocari D, Rahman AA, Pawling J, Zhang W, Sinha A, Rose CM, Isasa M, Zhang S, Wu R, Virtanen C, Hitomi T, Habu T, Sidhu SS, Koizumi A, Wilkins SE, Kislinger T, Gygi SP, Schofield CJ, Dennis JW, Wouters BG, Neel BG.
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Journal Title
Nat Cell Biol
Volume: 18
Issue: 7
Pages: 803-813
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] RNF213 is associated with Intracranial Aneurysms in the French-Canadian population.2016
Author(s)
Zhou S, Ambalavanan A, Rochefort D, Xie P, Bourassa CV, Hince P, Dionne-Laporte A, Spiegelman D, Gan-Or Z, Mirarchi C, Zaharieva V, Dupré N, Kobayashi H, Hitomi T, Harada K, Koizumi A, Xiong L, Dion PA, Rouleau GA.
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Journal Title
Am J Hum Genet
Volume: 99(5)
Issue: 5
Pages: 1072-1085
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Biochemical and Functional Characterization of RNF213 (Mysterin) R4810K, a Susceptibility Mutation of Moyamoya Disease, in Angiogenesis In Vitro and In Vivo.2015
Author(s)
Kobayashi H, Matsuda Y, Hitomi T, Okuda H, Shioi H, Matsuda T, Imai H, Sone M, Taura D, Harada KH, Habu T, Takagi Y, Miyamoto S, Koizumi A.
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Journal Title
J Am Heart Assoc.
Volume: 30;4(7)
Issue: 7
DOI
Related Report
Peer Reviewed / Open Access
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