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是小的22个核苷酸长的非编码RNA，可通过与靶基因的3 UTR结合来调节基因表达，从而导致抑制蛋白质翻译并降低mRNA稳定性。 在这里，我们假设microRNA调节哮喘的发病机理。 利用肺microRNA转录组的基因组宽屏幕来鉴定在房屋粉尘螨诱导的哮喘的实验鼠模型中的表达改变的microRNA。 另外，评估了皮质类固醇治疗对microRNA表达的影响。 正在进行的工作是针对产生有条件表达或删除肺部细胞中候选microRNA基因的小鼠。 我们已经产生了一种过表达候选microRNA基因之一的转基因小鼠，该基因目前正在用来表征其在哮喘发病机理中的作用。 我们还创建了一个质粒，以生成一个条件敲除小鼠的额外候选microRNA基因，该基因可能调节哮喘的致病表现。