MicroRNA-126a-5p enhances myocardial ischemia-reperfusion injury through suppressing Hspb8 expression.
MicroRNA-126a-5p enhances myocardial ischemia-reperfusion injury through suppressing Hspb8 expression.
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MicroRNA-126a-5p通过抑制Hspb8表达增强心肌缺血再灌注损伤
DOI：
10.18632/oncotarget.21613
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发表时间：
2017-11-07
期刊：
影响因子：
--
通讯作者：
Xiao X
中科院分区：
文献类型：
--
作者：
Jiang B;Liu Y;Liang P;Li Y;Liu Z;Tong Z;Lv Q;Liu M;Xiao X
先前研究发现，心肌缺血再灌注（M-I/R）损伤与多个基因有关。在本报告中，我们首先建立了M-I/R损伤的小鼠模型，并通过高通量microRNA表达分析证明microRNA-126 a-5 p与M-I/R损伤相关。我们进一步研究了microRNA-126 a-5 p在小鼠M-I/R损伤过程中的表达和功能。我们在M-I/R小鼠中观察到microRNA-126 a-5 p的高表达，以及血清中LDH和CK-MB（损伤标志物）水平的升高。H2 O2和缺氧/复氧（H/R）处理显著增加H9 C2细胞microRNA-126 a-5 p的表达，并呈浓度和时间依赖性。此外，microRNA-126 a-5 p在H9 C2细胞中的过表达抑制细胞活力，但增加LDH释放和caspase 3活性。基于血液动力学参数测量的心脏功能分析表明，M-I/R损伤小鼠中的microRNA-126 a-5 p表达消除导致M-I/R损伤引起的症状逆转。经食管超声心动图显示，与对照组相比，microRNA-126 a-5 p抑制剂治疗后M-I/R损伤小鼠的LVIDd和LVID值降低，LVFS%和LVEF%值升高。生物信息学分析表明，心肌保护蛋白Hspb 8是microRNA-126 a-5 p的靶点。这些结果表明，microRNA-126 a-5 p在小鼠M-I/R模型中表达上调，并通过抑制Hspb 8的表达促进了体内M-I/R损伤，这可能为M-I/R损伤的潜在治疗靶点的开发提供线索。
Previously, we found several genes are involved in myocardial ischemia-reperfusion (M-I/R) injury. In this report, we first developed a mouse model of M-I/R injury and demonstrated microRNA-126a-5p was associated with the M-I/R injury by using high-throughput microRNA expression analysis. We further investigated the expression and function of microRNA-126a-5p during mouse M-I/R injury. We observed high expression of microRNA-126a-5p in the M-I/R mice and increased levels of LDH and CK-MB (damage markers) in the serum. H2O2 and hypoxia/reoxygenation (H/R) treatment significantly increased the expression of microRNA-126a-5p in H9C2 cells in concentration- and time-dependent manners. Moreover, microRNA-126a-5p overexpression in H9C2 cells inhibited cell viability but increased LDH release and caspase 3 activity. Cardiac function analysis based on the measurements of hemodynamic parameters showed that microRNA-126a-5p expression ablation in M-I/R injured mice led to the reversal of the symptoms caused by M-I/R injury. Transesophageal echocardiography also revealed that the values of LVIDd and LVIDs were decreased while the values of LVFS% and LVEF% were increased in M-I/R injured mice after treatment with microRNA-126a-5p inhibitor, compared with the M-I/R injured mice treated with the control. Bioinformatic analysis demonstrated that Hspb8, a protective protein in myocardium, was the target of microRNA-126a-5p. Thus, these findings indicated that microRNA-126a-5p was up-regulated in mouse M-I/R model and promoted M-I/R injury in vivo through suppressing the expression of Hspb8, which may shed light on the development of potential therapeutic target for M-I/R injury.
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作者：
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影响因子：
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