Regulation of microRNA-302a in human and mouse macrophages after stimulation with modified low density lipoproteins. The main focus of the research is to explore whether microRNA-302a contributes to the maintenance of cholesterol homeostasis and therefore

修饰低密度脂蛋白刺激后人和小鼠巨噬细胞中 microRNA-302a 的调节。

• 批准号: 220300215
• 负责人: Dr. Svenja Meiler
• 金额: --
• 依托单位: Center for Cardiovascular Research
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/220300215?language=en
• 关键词: Regulation; microRNA; 302a; human; mouse

Cholesterol and other lipids play key roles in many physiological processes. Aberrant cholesterol/lipid homeostasis has been linked to a number of diseases including atherosclerosis. Therefore control of cholesterol levels is essential to human health. In addition to classical transcription regulators, a class of small endogenous double-stranded RNAs termed microRNAs (miRs) has emerged as important modulators of many cellular and physiological processes that affect organism growth, development, homeostasis, and disease. Recent studies have shown that specific miRs are regulated in modified low-density lipoprotein-treated macrophages, which can affect the cholesterol homeostasis in the cell. However involvement of miR-302a in lipid metabolism in macrophages has not been investigated so far. The aim of this study is to determine the potential role of miR-302a on the expression of genes involved in cellular cholesterol transport of mouse and human macrophages. To identify target genes of miR-302a and to manipulate miR-302a expression to regulate those genes in vitro assays will be used. To indicate the influence of miR-302a regarding cellular cholesterol transport and further more atherosclerosis in vivo experiments will be carried out. In this way miR-302a could be identified as an important therapeutic target for suppressing atherogenesis.

胆固醇和其他脂质在许多生理过程中起着关键作用。胆固醇/脂质稳态异常与包括动脉粥样硬化在内的许多疾病有关。因此，控制胆固醇水平对人体健康至关重要。除了经典的转录调节因子外，一类称为microRNA（miR）的小的内源性双链RNA已经成为影响生物体生长、发育、稳态和疾病的许多细胞和生理过程的重要调节因子。最近的研究表明，特定的miR在修饰的低密度脂蛋白处理的巨噬细胞中受到调节，这可以影响细胞中的胆固醇稳态。然而，miR-302 a在巨噬细胞中的脂质代谢中的参与迄今尚未被研究。本研究的目的是确定miR-302 a对参与小鼠和人巨噬细胞细胞胆固醇转运的基因表达的潜在作用。为了鉴定miR-302 a的靶基因并操纵miR-302 a表达以调节这些基因，将使用体外测定。为了表明miR-302 a对细胞胆固醇转运和进一步的动脉粥样硬化的影响，将进行体内实验。通过这种方式，miR-302 a可以被鉴定为抑制动脉粥样硬化形成的重要治疗靶点。