Pro-inflammatory activation of human macrophages regulated by lncRNAs

lncRNA调控人巨噬细胞的促炎激活

基本信息

批准号：
10199025
负责人：
Masanori Aikawa
金额：
$ 72.5万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
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/10199025
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

项目摘要

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.

项目概要巨噬细胞激活会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。本研究将建立一种系统方法，包括计算预测分析、多组学、网络科学以及体外和体内验证，发现长非编码 RNA (lncRNA) 介导的促炎症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 及其相互作用蛋白并开发计算分析来预测人类调节巨噬细胞激活的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激活中的作用。研究结果将有助于识别新的巨噬细胞激活机制，可能为新疗法提供分子基础。