Development of New Treatment Strategies of Cardiovascular Pathologies by Using Epigenetic Regulation
利用表观遗传调控开发心血管病理新治疗策略
基本信息
- 批准号:20390219
- 负责人:
- 金额:$ 11.81万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (B)
- 财政年份:2008
- 资助国家:日本
- 起止时间:2008 至 2010
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The pathogenesis of lifestyle diseases such as cardiovascular disease is more closely related to environmental factors than genetic factors. In other words, the changes in gene function and cellular phenotype lacking any changes in genomic sequence, known as epigenetic regulation, is considered to be responsible for the pathogenesis. Epigenetic regulation in the cardiovascular system, however, has not been sufficiently understood. We expected that the changes in chromatin structure would lead us towards a greater understanding of the mechanism of regulation of transcription in eukaryotes and discovered the interactions between DNA binding proteins and chromatin structural changes and their functional significance. We hypothesized that by focusing on cardiovascular epigenetic regulation, this study will explain how transcription in chromatin and DNA repair is regulated in cardiovascular disease and will contribute to drug discovery. In order to address epigenetic regulation in cardiovas … More cular disease, we studied KLF5, a key factor of this disease, and discovered molecules, such as ANP32B, which interact with KLF5. In addition to these interactive factors, we analyzed the function of ATM and H2AX, the key factors for DNA repair that we considered were important, by employing molecular biological and genetic engineering techniques (e.g. the generation of knockout mice) and disease animal models (e.g. vascular senescence models). As a result, (i) by examining the regulation of the histone chaperone family, we found a novel histone chaperone ANP32B, and its structural analysis revealed that ANP32B regulates the amount of histone in the promoter region of KLF5 downstream genes (Munemasa et al.2008). We also solved the crystal structure of (Tochio et al.2010). (ii) The analysis of the new regulative mechanism of vascular senescence by ATM showed that ATM plays an important role in oxidative stress-induced endothelial dysfunction and premature senescence through the Akt/p53/p21 pathway. Our research revealed the molecular mechanisms of epigenetic regulation in human pathology. Importantly, it is possible that these mechanisms may lead to new treatments, and new studies based on our results. Less
心血管疾病等生活方式疾病的发病机制与环境因素的关系比遗传因素更密切。换句话说,基因功能和细胞表型的变化,缺乏基因组序列的任何变化,称为表观遗传调控,被认为是发病机制的原因。然而,心血管系统中的表观遗传调控尚未得到充分理解。我们期望染色质结构的变化将引导我们对真核生物转录调控机制有更深入的了解,并发现DNA结合蛋白与染色质结构变化之间的相互作用及其功能意义。我们假设,通过专注于心血管表观遗传调控,这项研究将解释如何在染色质和DNA修复转录调节心血管疾病,并将有助于药物发现。为了解决心血管中的表观遗传调控, ...更多信息 我们研究了这种疾病的关键因子KLF 5,并发现了与KLF 5相互作用的分子,如ANP 32 B。除了这些相互作用的因素,我们分析了ATM和H2 AX的功能,我们认为是重要的DNA修复的关键因素,通过使用分子生物学和基因工程技术(如敲除小鼠的产生)和疾病动物模型(如血管衰老模型)。结果,(i)通过检查组蛋白伴侣蛋白家族的调节,我们发现了一种新的组蛋白伴侣蛋白ANP 32 B,其结构分析表明,ANP 32 B调节KLF 5下游基因启动子区域中组蛋白的量(Munemasa et al.2008)。我们还解决了(Tochio等人,2010)的晶体结构。(ii)对ATM调控血管衰老新机制的分析表明,ATM通过Akt/p53/p21通路在氧化应激诱导的内皮功能障碍和血管早衰中发挥重要作用。我们的研究揭示了人类病理学中表观遗传调控的分子机制。重要的是,这些机制可能会导致新的治疗方法,以及基于我们结果的新研究。少
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Molecular markers for cardiovascular disease : cardiovascular biomarkers to proteomic discovery.
心血管疾病的分子标记:心血管生物标记到蛋白质组学的发现。
- DOI:
- 发表时间:2008
- 期刊:
- 影响因子:0
- 作者:鈴木亨;永井良三
- 通讯作者:永井良三
Current approaches to aortic dissection ; from biomarkers to the international registry of acute aortic dissection (IRAD).
目前主动脉夹层的治疗方法;
- DOI:
- 发表时间:2009
- 期刊:
- 影响因子:0
- 作者:山本博幸;山岡聡;宮本千絵;井伊正則;日崎恵一;田沼徳真;宮本伸樹;奥田博介;足立靖;佐々木茂;有村佳昭;今井浩三;篠村恭久;鈴木亨
- 通讯作者:鈴木亨
Ataxia Telangiectasia Mutated (ATM)-mediated DNA Damage Response in Oxidative Stress-induced Vascular Endothelial Cell Senescence*
- DOI:10.1074/jbc.m110.125138
- 发表时间:2010-07
- 期刊:
- 影响因子:0
- 作者:Hong Zhan;Toru Suzuki;K. Aizawa;K. Miyagawa;R. Nagai
- 通讯作者:Hong Zhan;Toru Suzuki;K. Aizawa;K. Miyagawa;R. Nagai
Epigenetic regulation of chromatin transcription-KLFs as a model system.
染色质转录的表观遗传调控-KLFs作为模型系统。
- DOI:
- 发表时间:2010
- 期刊:
- 影响因子:0
- 作者:Satoshi Kobayashil;Hirohiko Ise;Masafumi Takahashil;Mitsuaki Goto;Shinichi Aso;Uichi Ikeda;鈴木亨
- 通讯作者:鈴木亨
Epigenetic control of gene transcription at the chromatin level with a focus on Kruppel-like factors.
染色质水平基因转录的表观遗传控制,重点关注 Kruppel 样因子。
- DOI:
- 发表时间:2008
- 期刊:
- 影响因子:0
- 作者:Suzuki T;Aizawa K;Munemasa Y;Matsumura T;Sawaki D;Kada N;Nagai R
- 通讯作者:Nagai R
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SUZUKI Toru其他文献
Doctoral Students in the American Research Universities: the Difference by Major Field: An Analysis of the Doctoral Student Survey 2006 by the National Research Council
美国研究型大学的博士生:专业领域差异:国家研究委员会2006年博士生调查分析
- DOI:
10.1109/iiai-aai.2018.00094 - 发表时间:
2018 - 期刊:
- 影响因子:0
- 作者:
SUZUKI Toru;TAKEDA Atsushi;TAKADAYA Yoko;FUJII Yoshihiro;Kenji MIWA;Soichiro Aihara - 通讯作者:
Soichiro Aihara
A Study about the Instruction for Master Thesis and Research Papers for "Experience Reflection" in Graduate Schools in Japan
日本研究生院硕士论文和研究论文“经验反思”指导研究
- DOI:
- 发表时间:
2019 - 期刊:
- 影响因子:0
- 作者:
SUZUKI Toru;TAKEDA Atsushi;TAKADAYA Yoko;FUJII Yoshihiro;Kenji MIWA - 通讯作者:
Kenji MIWA
学校規模ポジティブ行動支援(SWPBS)が公立中学校における問題行動発生率に及ぼす効果 ―4年間にわたる実行度の変化と問題行動発生率の推移―
全校积极行为支持(SWPBS)对公立初中问题行为发生率的影响 -4年来实施水平的变化和问题行为发生率的变化-
- DOI:
- 发表时间:
2023 - 期刊:
- 影响因子:0
- 作者:
SUZUKI Toru;FUJII Yoshihiro;MAEBARA Kazuaki;TAKEDA Atsushi;谷川雄一・庭山和貴 - 通讯作者:
谷川雄一・庭山和貴
Questionnaire Survey on the Prevalence of Selective Mutism at Special Needs Schools for Students with Intellectual Disability in Japan
关于日本智障学生特殊需要学校选择性沉默症患病率的问卷调查
- DOI:
10.14391/ajhs.22.101 - 发表时间:
2022 - 期刊:
- 影响因子:0
- 作者:
SUZUKI Toru;FUJII Yoshihiro;MAEBARA Kazuaki;TAKEDA Atsushi - 通讯作者:
TAKEDA Atsushi
SUZUKI Toru的其他文献
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{{ truncateString('SUZUKI Toru', 18)}}的其他基金
高専と日本の教育の質保障を動かす~学修成果証明のためのスマートコントラクト開発
提高技术学院和日语教育的质量保证 - 开发用于证明学习成果的智能合约
- 批准号:
19H00175 - 财政年份:2019
- 资助金额:
$ 11.81万 - 项目类别:
Grant-in-Aid for Encouragement of Scientists
Elucidation of the mechanism of pathophysiology for precision medicine and development of companion diagnostics
阐明精准医学的病理生理学机制和伴随诊断的发展
- 批准号:
16H05115 - 财政年份:2016
- 资助金额:
$ 11.81万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Study on mechanism for freeze trelance of a leech Ozobranchus jantseanus and its application
水蛭Ozobranchus jantseanus的冷冻机制研究及其应用
- 批准号:
15H04577 - 财政年份:2015
- 资助金额:
$ 11.81万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Exploring Innovative Deviation at the Interface of Grammar and Semantic Interpretation
探索语法和语义解释界面的创新偏差
- 批准号:
24520528 - 财政年份:2012
- 资助金额:
$ 11.81万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Softening prediction based on recystalization of ice crystal during frozen storage of agricultural products
基于冰晶再结晶的农产品冻藏软化预测
- 批准号:
24380143 - 财政年份:2012
- 资助金额:
$ 11.81万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Elucidation of cardiovascular pathologies by regulating the processing of the peptide
通过调节肽的加工来阐明心血管病理学
- 批准号:
24659383 - 财政年份:2012
- 资助金额:
$ 11.81万 - 项目类别:
Grant-in-Aid for Challenging Exploratory Research
Elucidation of the cardiovascular disease by the innovative three-dimensional proteome analytical method
创新三维蛋白质组分析方法阐明心血管疾病
- 批准号:
23390204 - 财政年份:2011
- 资助金额:
$ 11.81万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
On the Creativity of Grammar in the Use of Unselected Objects
论未选对象使用中的语法创造性
- 批准号:
21520499 - 财政年份:2009
- 资助金额:
$ 11.81万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Analysis of the effects of cell growth and cell death regulation on tumor development using tumor mice models
利用肿瘤小鼠模型分析细胞生长和细胞死亡调节对肿瘤发展的影响
- 批准号:
21770001 - 财政年份:2009
- 资助金额:
$ 11.81万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
A Comparative Study of Generative Grammar and Cognitive Grammar Approaches to Event Structure
事件结构生成语法和认知语法方法的比较研究
- 批准号:
18520373 - 财政年份:2006
- 资助金额:
$ 11.81万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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