MicroRNAs in Kidney Progenitor Cells.

肾祖细胞中的 MicroRNA。

• 批准号: 8441046
• 负责人: JACQUELINE HO
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8441046
• 关键词: Algorithms; Apoptosis; Bioinformatics; Biological Models; Boston; Cell physiology; Cells; Child; Childhood; Complement; Data; Developmental Process; Embryo; Endowment; Equilibrium; Foundations; Functional disorder; Gene Expression; Grant; Health; Individual; Jordan; Kidney; Kidney Failure; Knowledge; Mentors; Messenger RNA; MicroRNAs; Modeling; Molecular; Nephrons; Organ Culture Techniques; Pediatric Hospitals; Phase; Phenotype; Physicians; Play; Population; Research; Role; Scientist; Small RNA; Stem cells; Testing; Transcript; Transgenic Mice; Transgenic Organisms; Work; abstracting; body system; career; embryonic stem cell; gain of function; gene repression; improved; interest; loss of function; medical schools; member; mouse model; nephrogenesis; novel; peptide analog; premature; pro-apoptotic protein; progenitor; self-renewal; small hairpin RNA

Project Summary/Abstract MicroRNAs (miRNAs) are a group of novel small RNAs that regulate gene expression via the post- transcriptional repression of specific target mRNAs. As a group, miRNAs play a key role in diverse developmental processes, and are required for the differentiation of embryonic stem cells; however the function of miRNAs during kidney development remains largely undefined. Our preliminary work indicates that the loss of miRNAs within the nephron progenitor compartment of the developing kidney results in a premature depletion of this population, and as a consequence, a marked decrease in nephron number. Furthermore, this is accompanied by elevated expression of the pro-apoptotic protein Bim (also known as Bcl-2L11) specifically in nephron progenitors, and an increase in apoptosis in this cell population. We propose that specific miRNAs promote the survival of nephron progenitors by regulating the expression of Bim, and that this mechanism represents a means of determining congenital nephron endowment during normal kidney development. Specific aim 1: To characterize the role of Bim (Bcl-2L11) in the survival of nephron progenitors during kidney development. Specific aim 2: To define the function of the miRNA clusters, mmu-miR-106b~25 and mmu- miR-17~92, in regulating Bim expression and nephron progenitors. Specific aim 3: To determine the functional role of mmu-miR-10a during kidney development. The work proposed in this grant will serve as the foundation for the PI's transition into an independent career as a physician-scientist in an academic pediatric renal division over the next two years. The mentored phase (K99) will occur at Children's Hospital Boston and Harvard Medical School under the guidance of Dr. Jordan Kreidberg.

项目摘要/摘要 microRNA（miRNA）是一组新型的小RNA，通过后调节基因表达 特定靶标mRNA的转录抑制。作为一个小组，miRNA在多元化中起着关键作用 发育过程，是分化胚胎干细胞所必需的；但是 肾脏发育过程中miRNA的功能在很大程度上不确定。我们的初步工作表明 发育中的肾脏肾脏祖细胞室内miRNA的损失导致过早 该人群的耗竭，结果是肾单位数的显着下降。此外，这个 伴随着促凋亡蛋白BIM的表达升高（也称为Bcl-2l11） 在肾单位祖细胞中，该细胞群中凋亡的增加。我们提出了特定的miRNA 通过调节BIM的表达来促进肾单位祖细胞的存活，并提出这种机制 代表一种在正常肾脏发育过程中确定先天性肾脏捐赠的一种手段。 具体目的1：表征BIM（Bcl-2l11）在肾脏祖细胞生存中的作用 发展。特定目标2：定义miRNA簇的功能，MMU-MIR-106B〜25和MMU- miR-17〜92，在调节BIM表达和肾单位祖细胞中。特定目标3：确定 MMU-MIR-10A在肾脏发育过程中的功能作用。本赠款中提出的工作将作为 PI过渡到独立职业的基础，是学术儿科的医师科学家 接下来的两年肾部门。指导阶段（K99）将发生在波士顿儿童医院和 哈佛医学院在乔丹·克里德伯格（Jordan Kreidberg）博士的指导下。