Identification and Characterization of microRNA Genes in Asthma

哮喘中 microRNA 基因的鉴定和表征

• 批准号: 8939833
• 负责人: Stewart Levine
• 金额: $ 35.45万
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8939833
• 关键词: Adrenal Cortex Hormones; Anti-Inflammatory Agents; Anti-inflammatory; Asthma; Binding; Cells; Functional RNA; Gene Expression; Gene Expression Profile; Gene Targeting; Genes; Goals; Knockout Mice; Lung; MicroRNAs; Modeling; Mus; Nucleotides; Pathogenesis; Plasmids; Proteins; Pyroglyphidae; Role; Severities; Transgenic Mice; Translations; Untranslated Regions; Work; genome wide association study; mRNA Stability

MicroRNAs are small, 22 nucleotide-long, non-coding RNAs that regulate gene expression via binding to the 3 UTR of target genes, which results in the suppression of protein translation and decreased mRNA stability. Here, we hypothesized that microRNAs modulate the pathogenesis of asthma. A genome wide screen of the lung microRNA transcriptome was utilized to identify microRNAs whose expression is altered in an experimental murine model of house dust mite-induced asthma. In addition, the effect of corticosteroid treatment on microRNA expression was assessed. Ongoing work is directed at generating mice that conditionally express or delete candidate microRNA genes in lung cells. We have generated a transgenic mouse that over-expresses one of the candidate microRNA genes, which is currently being utilized to characterize its role in the pathogenesis of asthma. We have also created a plasmid to generate a conditional knock-out mouse for an additional candidate microRNA gene that may modulate the pathogenic manifestations of asthma.

MicroRNA是一种长度为22个核苷酸的非编码小RNA，通过与靶基因的3个UTR结合来调节基因表达，从而抑制蛋白质翻译和降低mRNA稳定性。 在这里，我们假设microRNA调节哮喘的发病机制。 利用肺microRNA转录组的全基因组筛选来鉴定其表达在室内尘螨诱导的哮喘的实验小鼠模型中改变的microRNA。 此外，还评估了皮质类固醇治疗对microRNA表达的影响。 正在进行的工作旨在产生在肺细胞中有条件地表达或删除候选microRNA基因的小鼠。 我们已经产生了一个转基因小鼠，过表达的候选microRNA基因之一，这是目前被用来表征其在哮喘发病机制中的作用。 我们还创建了一个质粒，以产生一个额外的候选microRNA基因的条件性敲除小鼠，该基因可能调节哮喘的致病表现。