MicroRNA-21 protects against the H(2)O(2)-induced injury on cardiac myocytes via its target gene PDCD4.
MicroRNA-21 protects against the H(2)O(2)-induced injury on cardiac myocytes via its target gene PDCD4.
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DOI：
10.1016/j.yjmcc.2009.01.008
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发表时间：
2009-07
影响因子：
5
通讯作者：
Zhang, Chunxiang
中科院分区：
文献类型：
--
作者：
Cheng, Yunhui;Liu, Xiaojun;Zhang, Shuo;Lin, Ying;Yang, Jian;Zhang, Chunxiang
活性氧通过多个基因表达的改变诱导心肌细胞损伤，在许多心脏疾病的发病机制中起着关键作用。microRNA（miRNAs）是一类新型的内源性小分子非编码RNA，通过降解或抑制靶mRNA的翻译来负调控细胞中约30%的基因。目前，ROS对miRNA表达的影响以及miRNA在ROS介导的心肌细胞损伤中的作用尚不清楚。使用定量实时RT-PCR（qRT-PCR），我们证明了过氧化氢（H2 O2）处理后，心肌细胞中microRNA-21（miR-21）上调。为了确定miRNA在H2 O2介导的基因调控和细胞损伤中的潜在作用，miR-21表达被miR-21抑制剂下调，并被pre-miR-21上调。miR-21抑制剂可增加H2 O2诱导的心肌细胞死亡和凋亡，而pre-miR-21可降低H2 O2诱导的心肌细胞死亡和凋亡。程序性细胞死亡4（PDCD 4）受miR-21调控，是miR-21在心肌细胞中的直接靶点。在H2 O2处理的心肌细胞中，通过腺病毒介导的无miR-21结合位点的PDCD 4过表达，抑制了pre-miR-21介导的对心肌细胞损伤的保护作用。此外，激活蛋白1（AP-1）是PDCD 4的下游信号分子，参与miR-21介导的对心肌细胞的作用。结果表明，miR-21对H2 O2刺激敏感。miR-21参与H2 O2介导的心肌细胞基因调控和功能调节。miR-21可能在与ROS相关的心脏疾病如心肌肥大、心力衰竭、心肌梗死和心肌缺血/再灌注损伤中发挥重要作用。
Reactive oxygen species (ROS)-induced cardiac cell injury via expression changes of multiple genes plays a critical role in the pathogenesis of numerous heart diseases. MicroRNAs (miRNAs) comprise a novel class of endogenous, small, noncoding RNAs that negatively regulate about 30% of the genes in a cell via degradation or translational inhibition of their target mRNAs. Currently, the effects of ROS on miRNA expression and the roles of miRNAs in ROS-mediated injury on cardiac myocytes are uncertain. Using quantitative real-time RT-PCR (qRT-PCR), we demonstrated that microRNA-21 (miR-21) was upregulated in cardiac myocytes after treatment with hydrogen peroxide (H2O2). To determine the potential roles of miRNAs in H2O2-mediated gene regulation and cellular injury, miR-21 expression was downregulated by miR-21 inhibitor and upregulated by pre-miR-21. H2O2-induced cardiac cell death and apoptosis were increased by miR-21 inhibitor and was decreased by pre-miR-21. Programmed cell death 4 (PDCD4) that was regulated by miR-21 and was a direct target of miR-21 in cardiac myocytes. Pre-miR-21-mediated protective effect on cardiac myocyte injury was inhibited in H2O2-treated cardiac cells via adenovirus-mediated overexpression of PDCD4 without miR-21 binding site. Moreover, Activator protein 1 (AP-1) was a downstream signaling molecule of PDCD4 that was involved in miR-21-mediated effect on cardiac myocytes. The results suggest that miR-21 is sensitive to H2O2 stimulation. miR-21 participates in H2O2-mediated gene regulation and functional modulation in cardiac myocytes. miR-21 might play an essential role in heart diseases related to ROS such as cardiac hypertrophy, heart failure, myocardial infarction, and myocardial ischemia/reperfusion injury.
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