The Role of MicroRNA in Placental Differentiation

MicroRNA 在胎盘分化中的作用

• 批准号: 7624105
• 负责人: Yoel Sadovsky
• 金额: $ 15.6万
• 依托单位: MAGEE-WOMEN'S RES INST AND FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7624105
• 关键词: Apoptotic; Biology; Cardiac; Cell Hypoxia; Cell Proliferation; Cell physiology; Cells; Chorionic villi; Complex; Condition; Cues; Development; Disease; Embryo; Fetal Development; First Pregnancy Trimester; Foundations; Functional RNA; Functional disorder; Funding; Gene Expression; Gene Silencing; Genes; Genetic Transcription; Glean; Growth and Development function; Heterochromatin; Homeostasis; Human; Hypoxia; Injury; Light; Maintenance; Metabolism; Methodology; MicroRNAs; Molds; Molecular; Mus; Organ; Organism; Pathway interactions; Pattern; Perfusion; Personal Satisfaction; Phenotype; Placenta; Placentation; Positioning Attribute; Pregnancy; Process; RNA; RNA Interference; Research; Research Project Grants; Role; Series; Shapes; Sheep; Signal Transduction; Small Interfering RNA; Standards of Weights and Measures; Surface; Testing; Third Pregnancy Trimester; Tissues; Transcript; Transcriptional Regulation; Translational Research; Translations; Trees; Villous; Work; cell injury; concept; design; human disease; implantation; innovation; novel; response; response to injury; stem; trophoblast

DESCRIPTION (provided by applicant): A precise and well-orchestrated set of molecular and cellular signals governs the differentiation and function of the luman placenta. Surfacing the placental villi, the trophoblast bilayer of the human placenta is well positioned to execute a series of functions that are essential for placental metabolism, and consequently facilitate fetal development. Whereas recent studies illuminated spatial and temporal pathways that influence transcriptional regulation of trophoblast genes in mouse, sheep and human placentas, little is known about the integration of these signals into maintenance of trophoblast tiomeostasis and placental adaptation to injury. Practically unknown five years ago, microRNAs (miRNAs) are ubiquitously expressed in tissues of diverse organisms, from worms to humans. As a part of the endogenous RNA silencing machinery, these short RNA strands act in concert with the RNA interference silencing complex to degrade target transcripts and silence translation, and thereby regulate development and maintain homeostasis. Moreover, dysregulated miRNA expression has been implicated in human diseases. We and others have recently shown that both the mouse and human placentas express miRNAs, yet their pattern of expression and function are unknown. Considering the fundamental role of the placenta in development of the mammalian embryo, as well as the profound consequences of placental dysfunction, it is paramount to investigate the function of miRNAs in this organ. This exploratory translational research project, which bridges recently discovered miRNA pathways to human trophoblast biology and disease, matches the R21 funding objectives. In the proposed work we will test the hypothesis that discrete miRNA species are expressed in human trophoblasts and regulate normal placental function as well as adaptive response to hypoxic injury. Information gleaned from our studies will likely shed light on novel mechanisms that govern trophoblast adaptive response to injury, and uncover the role of endogenous RNAi in the differentiation and function of the human placenta.

描述（由申请人提供）：一组精确且精心编排的分子和细胞信号控制鲁曼胎盘的分化和功能。人胎盘的滋养层双层位于胎盘绒毛表面，能够执行一系列对胎盘代谢至关重要的功能，从而促进胎儿发育。尽管最近的研究阐明了影响小鼠、绵羊和人类胎盘滋养层基因转录调控的空间和时间途径，但对这些信号整合到滋养层细胞稳态维持和胎盘对损伤的适应中知之甚少。五年前，microRNAs（miRNAs）几乎不为人所知，它在从蠕虫到人类的各种生物体的组织中普遍表达。作为内源性RNA沉默机制的一部分，这些短RNA链与RNA干扰沉默复合物协同作用以降解靶转录物并沉默翻译，从而调节发育并维持稳态。此外，miRNA表达失调与人类疾病有关。我们和其他人最近发现，小鼠和人类胎盘都表达miRNA，但它们的表达模式和功能尚不清楚。考虑到胎盘在哺乳动物胚胎发育中的基本作用，以及胎盘功能障碍的深远后果，研究miRNA在该器官中的功能至关重要。这个探索性的转化研究项目，将最近发现的miRNA通路与人类滋养层生物学和疾病联系起来，符合R21的资助目标。在拟议的工作中，我们将测试的假设，离散的miRNA物种在人类滋养层细胞表达，并调节正常的胎盘功能，以及适应性反应缺氧损伤。从我们的研究中收集的信息可能会揭示滋养层对损伤的适应性反应的新机制，并揭示内源性RNAi在人类胎盘分化和功能中的作用。