MicroRNA-24 inhibits high glucose-induced vascular smooth muscle cell proliferation and migration by targeting HMGB1
MicroRNA-24 inhibits high glucose-induced vascular smooth muscle cell proliferation and migration by targeting HMGB1
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MicroRNA-24通过靶向HMGB1抑制高糖诱导的血管平滑肌细胞增殖和迁移
DOI：
10.1016/j.gene.2016.04.027
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发表时间：
2016-07-25
期刊：
影响因子：
3.5
通讯作者：
Yang, Jun
中科院分区：
文献类型：
--
作者：
Yang, Jian;Chen, Lihua;Yang, Jun
血管平滑肌细胞（VSMCs）功能障碍在糖尿病血管疾病的发病机制中起着关键作用。最近的研究报道，microRNA-24 （miR-24）可能与糖尿病和动脉粥样硬化性血管疾病有关。本研究旨在探讨miR-24在模拟糖尿病的高糖条件下对VSMC增殖和迁移的作用，并揭示其潜在机制。从大鼠胸主动脉分离VSMCs，在孵育期间用正常葡萄糖（NG, 5.5 mM）或高葡萄糖（HG, 30 mM）处理。采用蒂班蓝染色法、BrdU掺入法和transwell室法检测细胞活力、增殖和迁移。分别用qRT-PCR和Western blot分析基因和蛋白的表达。我们还使用电泳迁移率转移法（EMSA）检测核因子κ B (nf - κ B) DNA结合。采用酶联免疫吸附法测定tnf - α和IL-6水平。结果表明，腺病毒介导的miR-24过表达显著抑制HG刺激的VSMC增殖和迁移。同时，作为miR-24靶点的高迁移率组盒1 （HMGB1）在转染miR-24后也被明显抑制。此外，nf - κ B核易位和DNA结合，tnf - α。和IL-6的产生均与HMGB1的下调相关。上述数据表明，miR-24是高糖诱导的VSMCs增殖和迁移的重要调节因子，并提示血管系统中miR-24的升高可能是预防糖尿病动脉粥样硬化发展的一种新的治疗策略。(C) 2016 Elsevier B.V.版权所有
Dysfunction of vascular smooth muscle cells (VSMCs) performs a key role in the pathogenesis of diabetic vascular disease. Recent studies have reported that microRNA-24 (miR-24) may be implicated in diabetes and atherosclerotic vascular diseases. This study was designed to explore the role of miR-24 on VSMC proliferation and migration under high glucose conditions mimicking diabetes, and reveal the underlying mechanism. VSMCs were isolated from rat thoracic aortas, treated with normal glucose (NG, 5.5 mM) or high glucose (HG, 30 mM) during an incubation period. Cell viability, proliferation and migration were detected by tiypan blue staining, BrdU incorporation assay and transwell chamber assay. Gene and protein expression were analyzed by qRT-PCR and Western blot respectively. We also used electrophoretic mobility shift assay (EMSA) to detect nuclear factor kappaB (NF-kappa B) DNA binding. TNF-alpha and IL-6 levels were determined by enzyme-linked immunosorbent assay. The results showed that adenovirus-mediated miR-24 overexpression significantly inhibited HG stimulated VSMC proliferation and migration. Meanwhile, high mobility group box-1 (HMGB1) as a target of miR-24, was also markedly suppressed after miR-24 transfection. Additionally, NF-kappa B nuclear translocation and DNA binding, TNF-alpha. and IL-6 production were all decreased associated with the down-regulation of HMGB1. The above data indicated that miR-24 is a crucial regulator of high glucose-induced proliferation and migration in VSMCs, and suggests that elevation of miR-24 in vascular system may be a novel therapeutic strategy to prevent the development of diabetic atherosclerosis. (C) 2016 Elsevier B.V. All rights reserved.