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：
8768569
负责人：
Ravi Goyal
金额：
$ 23.7万
依托单位：
LOMA LINDA UNIVERSITY
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 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8768569
关键词：
Adult Angiogenesis Inhibition Arteries Biological Assay Blood Vessels Blood capillaries Carotid Arteries Cells Chief Cell Code Complex Corneal Neovascularization Culture Media Custom Data Development Disease Dissection Endothelial Cells Epigenetic Process Fetal Development Fetus Fibroblasts Functional RNA Gene Expression Gene Expression Profile Gene Expression Regulation Gene Targeting Genes Genetic Genetic Transcription Goals Growth Hemangioma In Vitro Island Lead Life Malignant Neoplasms Mammals Molecular Movement Mus Newborn Infant Noise Oligonucleotide Microarrays Pathogenesis Pathway interactions Pattern Phase Phenotype Placental Insufficiency Play Pregnancy Process Proteins RNA Regenerative Medicine Regulation Regulatory Pathway Role Serum Sheep Smooth Muscle Myocytes Staging Technology Therapeutic Tissue Engineering Transcript Transcriptional Regulation Translational Regulation Tube Up-Regulation Wound Healing angiogenesis arteriole capillary cell type cerebral artery fetal fetal bovine serum gain of function innovation insight novel promoter public health relevance regenerative research study response tumor

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有关。重要的是，血管生成反应受血管生成基因的协调转录和翻译调节调节。在本提案中，我们将研究一种新的调节RNA分子的作用，称为长非编码RNA（LNCRNA）在胎儿和成人大脑动脉中血管生成的发育调控中的作用。在小鼠中的180,000多个转录本中，有20,000个是蛋白质编码基因，其余160,000个是lncRNA。这些lncRNA序列中的大多数都是较差的，并且被视为转录“噪声”。但是，lncRNA的一部分具有自己的启动子，并且在哺乳动物中是充分保守的。该组被称为长基因间非编码RNA（LincRNA）。该群体以在细胞分化，运动以及通过改变基因表达模式的细胞分化以及重编程中的有效分子转换而闻名。在血管生成中鉴定具有细胞和分子功能的LINCRNA将为发现新的调节途径提供一个令人兴奋的机会，从而可以更好地理解这一重要过程。因此，我们建议识别和表征lincRNA在通过发育调节血管生成中的作用。我们的具体目的将通过胎儿和成人卵巢脑动脉的功能筛查损失或增益来识别和分析与内皮激活有关的候选lincrNA。我们实验方法的基本原理是，它将允许仔细，特定于阶段的解剖来对lincrnas在血管生成和成熟过程中的变化中尚未表征的作用。它还具有对血管瘤，癌症的发病机理的见解，并有助于实现调节血管生成对再生医学和组织工程的潜力。