MicroRNAs in Endothelial Cell Activation.

MicroRNA 在内皮细胞激活中的作用。

• 批准号: 8469565
• 负责人: Yajaira Suarez
• 金额: $ 15.01万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2013-09-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8469565
• 关键词: Adhesions; Affect; Atherosclerosis; Biogenesis; Biological; Biological Assay; Biology; Blood Vessels; Cell Proliferation; Cell physiology; Cellular biology; Complex; Data; E-Selectin; Endothelial Cells; Fibroblast Growth Factor; Functional RNA; Gene Expression; Gene Expression Profile; Goals; Growth; Impaired wound healing; In Vitro; Inflammation; Inflammation Process; Inflammatory; Inflammatory Response; Intercellular adhesion molecule 1; Link; Mediating; Messenger RNA; MicroRNAs; Molecular; Oncogenic; Participant; Pathologic Processes; Pathway interactions; Physiological; Physiological Processes; Play; Process; Psoriasis; Regulation; Rheumatoid Arthritis; Role; Signal Pathway; Signal Transduction; Therapeutic; Transgenic Organisms; Tumor Necrosis Factor-alpha; VEGFA gene; Vascular Diseases; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factors; Vascular remodeling; Work; Wound Healing; angiogenesis; base; c-myc Genes; cell growth; cytokine; extracellular; gene repression; human DICER1 protein; in vivo; insight; loss of function; mouse model; programs; response; restenosis; tumor; tumor growth; tumorigenesis; wound

DESCRIPTION (provided by applicant): MicroRNAs (miRNAs) are short non-coding RNAs that control gene expression predominantly through post- transcriptional repression, implicated in the control of multiple physiological and pathological processes. Recently, we described roles for endothelial miRNAs in central aspects of vascular biology such as angiogenesis and inflammation, processes that require the coordination of numerous and complex signaling pathways in which endothelial cells (ECs) act as both active participants and regulators. Endothelial activation is essential for many vascular processes leading to inflammation, vascular remodeling and vessel growth. Cytokines, such as vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF) mediate this activation and play fundamental roles in the control of angiogenic and inflammatory responses, respectively. miRNA function is modulated by extracellular factors affecting their biogenesis or activity, thereby fine-tuning the regulation of biological responses. However, our understanding of the mechanisms governing the regulation of microRNA in ECs is limited. We postulate that physiological levels of miRNAs are regulated under conditions, such as inflammation or angiogenic activation, to coordinate specific gene expression programs in ECs. We propose three aims: Aim 1: To identify the molecular mechanisms whereby VEGF and TNF regulate miRNA levels in ECs. Aim 2: To examine the regulation of EC targets and functions by VEGF and TNF-regulated miRNA in vitro. Aim 3: To define the roles of VEGF and TNF- regulated miRNAs in vivo. In summary, completion of these aims will provide critical insight into fundamental regulatory mechanisms controlling endothelial miRNA biogenesis and activity and their impact on EC biology. Understanding the complex network involving EC miRNAs and their targets, leading to a coordinate pattern of gene expression undoubtedly will contribute to a better understanding of the cellular and molecular mechanisms that control EC activation and may identify potential therapeutic strategies for the regulation of endothelial activation through modulation of miRNA activity!

描述(申请人提供)：microRNAs(MiRNAs)是一种短的非编码RNA，主要通过转录后抑制来控制基因的表达，参与控制多种生理和病理过程。最近，我们描述了内皮miRNAs在血管生物学的中心方面所起的作用，如血管生成和炎症，这些过程需要众多复杂的信号通路的协调，在这些信号通路中，内皮细胞既是活跃的参与者，又是调节者。内皮激活在许多血管过程中是必不可少的，这些过程导致炎症、血管重塑和血管生长。血管内皮生长因子(VEGF)和肿瘤坏死因子(TNF)等细胞因子分别在血管生成和炎症反应的调控中起重要作用。MiRNA的功能受影响其生物发生或活性的细胞外因素的调节，从而微调生物反应的调节。然而，我们对内皮细胞中microRNA调控机制的理解是有限的。我们假设miRNAs的生理水平在炎症或血管生成激活等条件下受到调节，以协调内皮细胞中特定的基因表达程序。我们提出三个目标：目标1：确定血管内皮细胞生长因子和肿瘤坏死因子调节内皮细胞miRNA水平的分子机制。目的：研究血管内皮细胞生长因子和肿瘤坏死因子调节的miRNA对血管内皮细胞靶点和功能的影响。目的3：明确血管内皮生长因子和肿瘤坏死因子调节的miRNAs在体内的作用。综上所述，这些目标的完成将为控制内皮miRNA生物发生和活性的基本调控机制及其对EC生物学的影响提供关键的见解。了解涉及EC miRNAs及其靶点的复杂网络，导致基因表达的协调模式，无疑将有助于更好地理解控制EC激活的细胞和分子机制，并可能找到通过调节miRNA活性来调节内皮激活的潜在治疗策略！