Pro-inflammatory activation of human macrophages regulated by lncRNAs

lncRNA调控人巨噬细胞的促炎激活

• 批准号: 10428357
• 负责人: Masanori Aikawa
• 金额: $ 72.36万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10428357
• 关键词: Address; Biological; Biological Process; Biology; Blood; Blood Vessels; Cells; Communities; Complex; Computational Biology; Computer Analysis; Coronary Arteriosclerosis; Data; Development; Discipline; Disease; Drug usage; Endotoxemia; Event; Gene Expression Profiling; Goals; Hematopoietic Stem Cell Transplantation; Heterogeneity; Human; In Vitro; Inflammation; Inflammatory; Laboratories; Lesion; Leukocytes; Life; Link; Machine Learning; Macrophage Activation; Mechanics; Mediating; Methods; Molecular; Myocardial; NF-kappa B; Network-based; Outcome; Pathway Analysis; Patients; Plasma; Play; Protein Analysis; Proteins; Proteomics; RNA; Reporting; Residual state; Risk; Risk Factors; Role; Science; Signal Transduction; Small Interfering RNA; Splenocyte; System; Systems Biology; Tissues; Untranslated RNA; Validation; Vascular Diseases; arterial lesion; base; cytokine; experimental study; femoral artery; gain of function; global health; human disease; humanized mouse; in vivo; injured; loss of function; macrophage; modifiable risk; mouse model; multiple omics; network models; novel; novel therapeutics; overexpression; protein protein interaction; single cell analysis; tool; transcriptome; transcriptome sequencing; transcriptomics; vascular inflammation

Project Summary Macrophage activation promotes major inflammatory disorders, including arterial diseases. Its underlying mechanisms, however, remain obscure. The present study will establish a systems approach, involving computational prediction analyses, multi-omics, network science, and in vitro and in vivo validation, to discover long noncoding RNA (lncRNA)-mediated mechanisms for pro-inflammatory activation of macrophages and arterial disease. In Specific Aim 1, we will involve omics studies of human macrophages to identify lncRNAs and their interacting proteins and develop computational analyses to predict human lncRNAs that regulate macrophage activation. Specific Aim 2 will examine the functionality of candidate lncRNAs in macrophage activation in vitro and in vivo. The findings from the study will help to identify new mechanisms for macrophage activation and may provide molecular bases for new therapies.

项目摘要 巨噬细胞活化促进主要炎症性疾病，包括动脉疾病。其底层 然而，机制仍然模糊不清。本研究将确立一种系统方法， 计算预测分析，多组学，网络科学，体外和体内验证， 发现长链非编码RNA（lncRNA）介导的促炎激活机制， 巨噬细胞和动脉疾病。在具体目标1中，我们将涉及人类巨噬细胞的组学研究 识别lncRNA及其相互作用的蛋白质，并开发计算分析来预测人类 调节巨噬细胞活化的lncRNA。具体目标2将检查候选人的功能 lncRNA在体外和体内巨噬细胞活化中的作用。研究结果将有助于确定新的 巨噬细胞活化的机制，并可能为新的治疗提供分子基础。