MicroRNAs, cardiac function and cardiomyopathy

MicroRNA、心脏功能和心肌病

基本信息

批准号：
10559334
负责人：
Da-Zhi Wang
金额：
$ 1.22万
依托单位：
UNIVERSITY OF SOUTH FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-21 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10559334
关键词：
MicroRNAs cardiac function cardiomyopathy

项目摘要

Contact PD/PI: Wang, Da-Zhi Cardiovascular disease is the leading cause of death in United States. However, the molecular events that control heart development and cardiac function are not fully understood. MicroRNAs (miRNAs) are a class of small regulatory RNA molecules found in most organisms. Emerging evidence has established that miRNAs play important regulatory roles, mainly by degrading target messenger RNAs (mRNAs) and/or inhibiting translation of protein-coding mRNAs in a variety of biological processes, including cell proliferation, differentiation and survival. miRNAs are also implicated in many human diseases, including cardiovascular disease. The discovery of miRNAs and their potential biological functions in regulating gene expression opened a completely new field to investigate how miRNAs participate in “classical” gene expression pathways. To date, more than 2,000 miRNAs have been identified in humans; however, the molecular mechanisms and the in vivo functions of most miRNAs remain unknown. The overall goal of this study is to define the biological function and the molecular mechanisms of miRNAs in the heart. Our central hypothesis is that miRNAs are components of the molecular circuitry that controls cardiac gene expression and function. More specifically, we will test our hypothesis that the Trbp-miR-208a pathway regulates cardiac function is a context-dependent manner. We present three integrative aims to test our hypothesis: Aim #1. What is the function of Trbp in the heart under pathophysiological stresses? Aim #2. How is the specificity of Trbp function in the miRNA pathway defined in the heart? Aim #3. What is the role of miR-208a in the heart and how does it work? Our studies will provide important insights into the molecular mechanisms by which miRNAs control mammalian heart development, function and cardiac gene expression. The molecular strategies we uncover in these studies will help define the ontogenesis of heart failure with potential broader implications for understanding the pathophysiology of cardiac disease in humans. Project Summary/Abstract Page 6

联系PD/PI：Wang，da-zhi 心血管疾病是美国死亡的主要原因。但是，分子控制心脏发展和心脏功能的事件尚未完全了解。 microRNA（miRNA）是在大多数生物体中发现的一类小调节RNA分子。新兴证据已经确定，miRNA扮演着重要的调节作用，主要是由降解目标信使RNA（mRNA）和/或抑制蛋白质编码的翻译在各种生物过程中的mRNA，包括细胞增殖，分化和生存。许多人类疾病也实施了miRNA，包括心血管疾病。 MiRNA的发现及其在调节基因的潜在生物学功能表达开放了一个全新的领域，以调查miRNA如何参与“古典” 基因表达途径。迄今为止，在人类中已经确定了2,000多个miRNA。但是，大多数miRNA的分子机制和体内功能仍然存在未知。这项研究的总体目标是定义生物学功能和分子机制心脏中的miRNA。我们的中心假设是miRNA是控制心脏基因表达和功能的分子电路。更具体地说，我们将检验我们的假设，即TRBP-MIR-208A途径调节心脏功能是与上下文有关的方式。我们提出了三个综合目的，以检验我们的假设：目标＃1。在病理生理应力下，TRBP在心脏中的功能是什么？目标＃2。在miRNA途径中定义的miRNA途径中TRBP功能的特异性如何心？目标＃3。 miR-208a在心脏中的作用是什么？它如何起作用？我们的研究将提供有关miRNA的分子机制的重要见解控制哺乳动物心脏发育，功能和心脏基因表达。分子我们在这些研究中发现的策略将有助于定义心力衰竭的个体发生潜在的广播公司对理解心脏病的病理生理学的影响人类。项目摘要/摘要页面6

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Adeno-associated virus-mediated delivery of anti-miR-199a tough decoys attenuates cardiac hypertrophy by targeting PGC-1alpha.

DOI：
10.1016/j.omtn.2020.11.007
发表时间：
2021-03-05
期刊：
Molecular therapy. Nucleic acids
影响因子：
0
作者：
Yan H;Wang H;Zhu X;Huang J;Li Y;Zhou K;Hua Y;Yan F;Wang DZ;Luo Y
通讯作者：
Luo Y

Decreased miR-497-5p Suppresses IL-6 Induced Atrophy in Muscle Cells.

DOI：
10.3390/cells10123527
发表时间：
2021-12-14
期刊：
Cells
影响因子：
6
作者：
Freire PP;Cury SS;Lopes LO;Fernandez GJ;Liu J;de Moraes LN;de Oliveira G;Oliveira JS;de Moraes D;Cabral-Marques O;Dal-Pai-Silva M;Hu X;Wang DZ;Carvalho RF
通讯作者：
Carvalho RF

Deletion of miRNA-22 Induces Cardiac Hypertrophy in Females but Attenuates Obesogenic Diet-Mediated Metabolic Disorders.