MicroRNAs in Regulation of Pulmonary Vascular Smooth Muscle Cell Proliferation

尽管PAH的发病机制涉及许多基因，但PAH是一种如此复杂的疾病，以至于 可能有多个基因参与其中。这些基因可能受Key基因的影响。 监管机制。MicroRNAs(MiRNAs)是一种小的非编码内源RNA分子，由以下组成 大约21-25个新台币。MiRNAs通过其3‘-末端的互补序列识别其靶标 其mRNA的非翻译区(UTR)并形成RNA诱导的沉默复合体，导致部分 成熟信使核糖核酸的降解或翻译抑制。MiRNA途径在进化上是保守的， 调节细胞功能的许多方面，包括细胞周期、分化、增殖、存活和 新陈代谢。单个miRNAs可以调节多达数百个基因或蛋白质，使它们成为吸引人的靶标。 用于研究PAH的发病机制。在这项提案中，我们提出了三个相互关联的目标：目标1 确定并验证肺动脉平滑肌(PASMC)细胞miRNA表达的变化 来自PAH和对照组的肺组织；目标2是确定miR-143是否下调，以及 其靶标在PAH患者的PASMC和肺组织中的表达发生改变；目的3是为了确定 PASMC和肺组织中miR-17~92簇是否下调及其靶点是否上调 PAH患者。

Although many genes have been implicated in the pathogenesis of PAH, PAH is such a complex disease that there are probably multiple genes involved. It is possible that these genes are under the influence of key regulatory mechanisms. MicroRNAs (miRNAs) are small non-coding endogenous RNA molecules consisting of approximately 21-25 nt. miRNAs recognize their targets through complementary sequences in their 3'- untranslated regions (UTR) of their mRNA and form RNA-induced silencing complexes, leading to the partial degradation of mature mRNA or translation repression. miRNA pathways are evolutionarily conserved and regulate many aspects of cell functions including cell cycle, differentiation, proliferation, survival, and metabolism. Single miRNAs can regulate up to hundreds of genes or proteins, making them attractive targets for study in the pathogenesis of PAH. In this proposal, we propose three interrelated aims: Aim 1 is to determine and validate changes in miRNA expression in pulmonary arterial smooth muscle (PASMC) cells and lung tissue from PAH and control subjects; Aim 2 is to determine whether miR-143 is downregulated and the expression of its targets is altered in PASMC and lung tissues of PAH patients; and Aim 3 is to determine whether miR-17~92 cluster is downregulated and their targets are upregulated in PASMC and lung tissue of PAH patients.