GENETIC DISSECTION OF MICRORNA FUNCTION DURING HEART REGENERATION

心脏再生过程中微小RNA功能的基因剖析

• 批准号: 8360315
• 负责人: Viravuth P Yin
• 金额: $ 14.64万
• 依托单位: MOUNT DESERT ISLAND BIOLOGICAL LAB
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360315
• 关键词: Acute myocardial infarction; Adult; Biological Models; Cardiac; Cardiac Myocytes; Cells; Cicatrix; Collagen; Development; Dicer Enzyme; Dissection; Funding; Genetic; Genetic Models; Genetic Programming; Goals; Grant; Heart; Injury; Maine; MicroRNAs; Myocardial; Myocardium; National Center for Research Resources; Natural regeneration; Organism; Principal Investigator; Process; Research; Research Infrastructure; Resources; Role; Source; Tissues; Transgenic Organisms; United States National Institutes of Health; Zebrafish; comparative; cost; functional genomics; organ regeneration; programs; regenerative; repaired; response; restoration

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. In response to an acute myocardial infarction, the mammalian heart responds with formation of collagen-laden scar tissue. In contrast, the zebrafish heart will undergo cardiomyocyte (CM) proliferation to repair the damaged or missing portion of the myocardial wall, thereby enabling complete restoration of cardiac function. Why certain organisms are better equipped to regenerate lost and damaged tissue has been the subject of intense studies for over three centuries. Yet to date, we know very little about the genetics that stimulate organ regeneration. It is clear however, that the transformation from a differentiated tissue into highly proliferative and regenerative cells requires dramatic changes in developmental programs. In this proposal I will examine the contributions of microRNAs (miRNAs) as modulators of changes in genetic programs during heart regeneration by focusing on the role of the key processing enzyme, Dicer and two specific miRNAs, miR-21 and miR133. For my studies, I will use the powerful, vertebrate zebrafish as a genetic model system due to its robust capacity for heart regeneration. My goal for this research is to ascertain how tissue-specific miRNAs are regulating cardiac regeneration through the use of inducible transgenic strains that modify miRNA activity. My studies will enhance potential therapies to increase survival and regeneration of adult cardiac muscle following ischemic injury.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 为了应对急性心肌梗塞，哺乳动物心脏会形成富含胶原蛋白的疤痕组织。相比之下，斑马鱼心脏会进行心肌细胞（CM）增殖，以修复心肌壁受损或缺失的部分，从而使心脏功能完全恢复。为什么某些生物体能够更好地再生丢失和受损的组织，这一直是三个多世纪以来深入研究的主题。然而迄今为止，我们对刺激器官再生的遗传学知之甚少。然而，很明显，从分化组织转变为高度增殖和再生的细胞需要发育程序的巨大改变。在本提案中，我将通过重点关注关键加工酶 Dicer 和两种特定 miRNA miR-21 和 miR133 的作用，研究 microRNA (miRNA) 作为心脏再生过程中遗传程序变化调节剂的贡献。在我的研究中，我将使用强大的脊椎动物斑马鱼作为遗传模型系统，因为它具有强大的心脏再生能力。 我这项研究的目标是确定组织特异性 miRNA 如何通过使用可改变 miRNA 活性的诱导转基因菌株来调节心脏再生。 我的研究将增强潜在的治疗方法，以提高成人心脏的存活和再生能力 缺血性损伤后的肌肉。