GENETIC DISSECTION OF MICRORNA FUNCTION DURING HEART REGENERATION

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 在对急性心肌梗塞的反应中，哺乳动物心脏以形成充满胶原的瘢痕组织来反应。相反，斑马鱼心脏将经历心肌细胞（CM）增殖以修复心肌壁的受损或缺失部分，从而能够完全恢复心脏功能。为什么某些生物体能够更好地再生丢失和受损的组织，这是三个多世纪以来深入研究的主题。然而，到目前为止，我们对刺激器官再生的遗传学知之甚少。然而，很明显，从分化的组织转化为高度增殖和再生的细胞需要发育程序的巨大变化。在本提案中，我将通过关注关键加工酶Dicer和两种特异性miRNAs miR-21和miR 133的作用，研究microRNAs（miRNAs）作为心脏再生过程中遗传程序变化的调节剂的贡献。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。 本研究的目的是通过使用可诱导的转基因菌株来修饰miRNA的活性，以确定组织特异性miRNA是如何调节心脏再生的。 我的研究将增强潜在的治疗方法，以增加成人心脏的存活和再生。 缺血性损伤后的肌肉。

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.