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.

项目概要/摘要 MicroRNA (miRNA) 是一组新型小RNA，通过后处理调节基因表达。 特定目标 mRNA 的转录抑制。作为一个群体，miRNA 在多种方面发挥着关键作用 发育过程，并且是胚胎干细胞分化所必需的；然而 肾脏发育过程中 miRNA 的功能在很大程度上仍不清楚。我们的前期工作表明 发育中肾脏的肾单位祖细胞内 miRNA 的丢失会导致早产 该群体的消耗，导致肾单位数量显着减少。此外，这 伴随着促凋亡蛋白 Bim（也称为 Bcl-2L11）的表达升高 肾单位祖细胞中的细胞凋亡增加。我们建议特定的 miRNA 通过调节 Bim 的表达来促进肾单位祖细胞的存活，并且该机制 代表了正常肾脏发育过程中确定先天性肾单位禀赋的一种方法。 具体目标 1：表征 Bim (Bcl-2L11) 在肾脏移植过程中肾单位祖细胞存活中的作用 发展。具体目标 2：定义 miRNA 簇 mmu-miR-106b~25 和 mmu- 的功能 miR-17~92，调节Bim表达和肾单位祖细胞。具体目标 3：确定 mmu-miR-10a 在肾脏发育过程中的功能作用。这笔赠款中提议的工作将作为 为 PI 过渡为学术儿科医师科学家的独立职业奠定了基础 未来两年的肾分裂。指导阶段 (K99) 将在波士顿儿童医院进行 哈佛医学院在乔丹·克雷德伯格博士的指导下。