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首页> 外文期刊>Circulation journal >Vascular smooth muscle cell proliferation is influenced by let-7d microRNA and its interaction with KRAS.
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Vascular smooth muscle cell proliferation is influenced by let-7d microRNA and its interaction with KRAS.

机译:let-7d microRNA及其与KRAS的相互作用会影响血管平滑肌细胞的增殖。

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BACKGROUND: Several microRNAs (miRNAs) have been reported to regulate cardiovascular biological and pathological processes through inhibiting the translation of certain RNA transcripts. However, little is known about the association between miRNAs and vascular smooth muscle cell (VSMC) proliferation. The aim was to investigate the role of miRNAs in VSMC growth and the potential mechanism. METHODS AND RESULTS: Primary VSMCs were isolated from the medial layer of the thoracic aorta obtained from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). miRNA microarrays were used to analyze the difference in miRNA expression between VSMCs of SHR and WKY rats and were validated using TaqMan real-time PCR. Of the potentially related genes under the influence of let-7d identified through literature search, KRAS was verified by western blot and functionally analyzed using miRNA mimics transfection and analysis of transfectants by cell enumeration was made using CCK-8 and flow cytometric analysis of cell cycle progression. let-7d-transfected VSMCs from SHR, WKY and human coronary arteries expressed significantly lower amounts of KRAS protein, displayed reduced cell growth and led to a greater number of cells in the G1 phase than the G2/M phases of the cell cycle. CONCLUSIONS: let-7d was significantly downregulated in VSMCs as an important regulator of cell proliferation. RAS might be involved in the proliferation regulation by let-7d.
机译:背景:据报道,有几种微RNA(miRNA)通过抑制某些RNA转录物的翻译来调节心血管的生物学和病理过程。但是,关于miRNA与血管平滑肌细胞(VSMC)增殖之间的关联知之甚少。目的是研究miRNA在VSMC生长中的作用及其潜在机制。方法和结果:从自发性高血压大鼠(SHR)和Wistar Kyoto大鼠(WKY)的胸主动脉中层分离出原代VSMC。 miRNA芯片用于分析SHR和WKY大鼠的VSMC之间miRNA表达的差异,并使用TaqMan实时PCR进行了验证。在通过文献检索鉴定的let-7d影响下的潜在相关基因中,通过Western blot验证了KRAS,并使用miRNA模拟转染对功能进行了分析,并使用CCK-8通过细胞计数和细胞周期流式细胞分析对转染子进行了分析。进展。来自SHR,WKY和人冠状动脉的let-7d转染的VSMC表达的KRAS蛋白量显着降低,显示出细胞生长降低,并且导致G1期的细胞数量高于细胞周期的G2 / M期。结论:let-7d在VSMC中被显着下调,这是细胞增殖的重要调节剂。 RAS可能参与了let-7d的增殖调控。

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