Role of LincRNA in Developmental Regulation of Angiogenesis
LincRNA 在血管生成发育调控中的作用
基本信息
- 批准号:8885866
- 负责人:
- 金额:$ 19.26万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-07-10 至 2018-06-30
- 项目状态:已结题
- 来源:
- 关键词:AdultAngiogenesis InhibitionArteriesBiological AssayBlood VesselsBlood capillariesCarotid ArteriesCellsChief CellCodeComplexCorneal NeovascularizationCulture MediaCustomDataDevelopmentDiseaseDissectionEndothelial CellsEpigenetic ProcessFetal DevelopmentFetusFibroblastsGene ExpressionGene Expression ProfileGene Expression RegulationGene TargetingGenesGeneticGenetic TranscriptionGoalsGrowthHealthHemangiomaIn VitroIslandLeadLifeMalignant NeoplasmsMammalsMolecularMovementMusNewborn InfantNoiseOligonucleotide MicroarraysPathogenesisPathway interactionsPatternPhasePhenotypePlacental InsufficiencyPlayPregnancyProcessProteinsRNARegenerative MedicineRegulationRegulatory PathwayRoleSerumSheepSmooth Muscle MyocytesStagingTechnologyTherapeuticTissue EngineeringTranscriptTranscriptional RegulationTranslational RegulationTubeUntranslated RNAUp-RegulationWound Healingangiogenesisarteriolecapillarycell typecerebral arteryfetalfetal bovine serumgain of functioninnovationinsightnovelpromoterregenerativeresearch studyresponsetumor
项目摘要
DESCRIPTION (provided by applicant): Developmental maturation from fetus to adult is associated with changes in the angiogenic potential of arteries. Importantly, angiogenic response is regulated by a coordinated transcriptional and translational regulation of angiogenesis genes. In the present proposal, we will examine the role of a new class of regulatory RNA molecules known as long non-coding RNAs (lncRNAs) in developmental regulation of angiogenesis in fetus and adult cerebral arteries. Out of more than 180,000 transcripts in mouse, 20,000 are the protein coding genes and majorities of the remaining 160,000 are lncRNA. Most of these lncRNA sequences are poorly conserved and have been regarded as transcriptional "noise". However, a subset of lncRNA has its own promoter, and is well conserved in mammals. This group is known as long intergenic non-coding RNA (lincRNA). This group is known for acting as potent molecular switch in cellular differentiation, movement, as well as in reprogramming of cell states by altering gene expression patterns. Identification of lincRNAs with cellular and molecular functions in angiogenesis will provide an exciting opportunity to discover new regulatory pathways that may lead to a better understanding of this vital process. Thus, we propose to identify and characterize the role of lincRNAs in regulating angiogenesis with development. Our specific aims will identify and analyze candidate lincRNAs involved in endothelial activation by a loss or gain of function screen in fetal and adult ovine cerebral arteries. The rationale for our experimental approach is that it will allow a careful, stage-specific dissection of the yet uncharacterized roles of lincRNAs in angiogenesis and changes with maturation. It also has the potential to provide insights into the pathogenesis of hemangioma, cancer, as well as contribute in efforts to realize the potential of regulated angiogenesis for regenerative medicine and tissue engineering.
描述(由申请人提供):从胎儿到成人的发育成熟与动脉血管生成潜力的变化相关。重要的是,血管生成反应是通过血管生成基因的协调转录和翻译调节来调节的。在本提案中,我们将研究一类称为长非编码RNA(lncRNA)的新型调节RNA分子在胎儿和成人脑动脉血管生成的发育调节中的作用。在小鼠的 180,000 多个转录本中,20,000 个是蛋白质编码基因,其余 160,000 个中的大多数是 lncRNA。这些lncRNA序列大多数保守性较差,被视为转录“噪音”。然而,lncRNA 的一个子集有自己的启动子,并且在哺乳动物中非常保守。该组被称为长基因间非编码RNA (lincRNA)。该基团因在细胞分化、运动以及通过改变基因表达模式来重新编程细胞状态中充当有效的分子开关而闻名。鉴定在血管生成中具有细胞和分子功能的 lincRNA 将为发现新的调控途径提供令人兴奋的机会,从而更好地理解这一重要过程。因此,我们建议鉴定和表征 lincRNA 在调节血管生成和发育中的作用。我们的具体目标是通过胎儿和成年绵羊脑动脉功能丧失或获得的筛查来识别和分析参与内皮激活的候选 lincRNA。我们实验方法的基本原理是,它将允许对 lincRNA 在血管生成和成熟变化中尚未表征的作用进行仔细、阶段性的剖析。它还具有深入了解血管瘤、癌症的发病机制的潜力,并有助于实现再生医学和组织工程中调节血管生成的潜力。
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)
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William J. Pearce其他文献
The vascular neural network—a new paradigm in stroke pathophysiology
血管神经网络——中风病理生理学的一种新范例
- DOI:
10.1038/nrneurol.2012.210 - 发表时间:
2012-10-16 - 期刊:
- 影响因子:33.100
- 作者:
John H. Zhang;Jerome Badaut;Jiping Tang;Andre Obenaus;Richard Hartman;William J. Pearce - 通讯作者:
William J. Pearce
Mechanisms of platelet-induced angiospastic reactions: potentiation of calcium sensitivity.
血小板诱导的血管痉挛反应的机制:钙敏感性增强。
- DOI:
10.1139/y97-109 - 发表时间:
1997 - 期刊:
- 影响因子:2.1
- 作者:
Sergey E. Akopov;Lubo Zhang;William J. Pearce - 通讯作者:
William J. Pearce
Effects of maturation and acute hypoxia on receptor-IP(3) coupling in ovine common carotid arteries.
成熟和急性缺氧对绵羊颈总动脉受体-IP(3) 偶联的影响。
- DOI:
- 发表时间:
2001 - 期刊:
- 影响因子:0
- 作者:
D. Angeles;James M. Williams;Ralph E. Purdy;Lubo Zhang;William J. Pearce - 通讯作者:
William J. Pearce
William J. Pearce的其他文献
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{{ truncateString('William J. Pearce', 18)}}的其他基金
Gestational Hypoxia and Programming of Maternal, Fetal and Newborn Vascular Function
妊娠期缺氧与母体、胎儿和新生儿血管功能的编程
- 批准号:
10650166 - 财政年份:2020
- 资助金额:
$ 19.26万 - 项目类别:
Gestational Hypoxia and Programming of Maternal, Fetal and Newborn Vascular Function
妊娠期缺氧与母体、胎儿和新生儿血管功能的编程
- 批准号:
10188626 - 财政年份:2020
- 资助金额:
$ 19.26万 - 项目类别:
Gestational Hypoxia and Programming of Maternal, Fetal and Newborn Vascular Function
妊娠期缺氧与母体、胎儿和新生儿血管功能的编程
- 批准号:
10044704 - 财政年份:2020
- 资助金额:
$ 19.26万 - 项目类别:
Gestational Hypoxia and Programming of Maternal, Fetal and Newborn Vascular Function
妊娠期缺氧与母体、胎儿和新生儿血管功能的编程
- 批准号:
10455711 - 财政年份:2020
- 资助金额:
$ 19.26万 - 项目类别:
Mechanisms mediating age-dependent inhibition of cerebrovascular MLCK activity and contractility by chronic hypoxia
慢性缺氧对脑血管 MLCK 活性和收缩力的年龄依赖性抑制的介导机制
- 批准号:
9072345 - 财政年份:2016
- 资助金额:
$ 19.26万 - 项目类别:
Cerebrovascular Myosin Light Chain Phosphorylation in Fetus, Newborn, and Adult
胎儿、新生儿和成人的脑血管肌球蛋白轻链磷酸化
- 批准号:
8332242 - 财政年份:2011
- 资助金额:
$ 19.26万 - 项目类别:
Cerebrovascular Myosin Light Chain Phosphorylation in Fetus, Newborn, and Adult
胎儿、新生儿和成人的脑血管肌球蛋白轻链磷酸化
- 批准号:
8222072 - 财政年份:2011
- 资助金额:
$ 19.26万 - 项目类别:
Cerebrovascular Myosin Light Chain Phosphorylation in Fetus, Newborn, and Adult
胎儿、新生儿和成人的脑血管肌球蛋白轻链磷酸化
- 批准号:
8448654 - 财政年份:2011
- 资助金额:
$ 19.26万 - 项目类别:
Cerebrovascular Myosin Light Chain Phosphorylation in Fetus, Newborn, and Adult
胎儿、新生儿和成人的脑血管肌球蛋白轻链磷酸化
- 批准号:
8640992 - 财政年份:2011
- 资助金额:
$ 19.26万 - 项目类别:
Role of Vascular Endothelial Growth Factor in Hypoxic Remodeling of Ovine Cer
血管内皮生长因子在绵羊神经细胞缺氧重塑中的作用
- 批准号:
8015754 - 财政年份:2010
- 资助金额:
$ 19.26万 - 项目类别:
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