MicroRNA 181b promotes vascular smooth muscle cells proliferation through activation of PI3K and MAPK pathways.
MicroRNA 181b promotes vascular smooth muscle cells proliferation through activation of PI3K and MAPK pathways.
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发表时间：
2015-09
影响因子：
1.4
通讯作者：
Tie-Jun Li;Yan-Li Chen;C. Gua;Sheng-Jiang Xue;Shu-Mei Ma;Xiao-dong Li
中科院分区：
文献类型：
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作者：
Tie-Jun Li;Yan-Li Chen;C. Gua;Sheng-Jiang Xue;Shu-Mei Ma;Xiao-dong Li
血管平滑肌细胞（VSMCs）增生是病理性心血管事件如再狭窄和动脉粥样硬化的共同特征。microrna （miRs）在VSMCs增殖中的作用和机制尚不清楚。在这里，我们报道miR-181b促进VSMCs的增殖和迁移。在动物模型中，球囊导管损伤后，miR-181b在大鼠颈动脉中显著升高。将miR-181b抑制剂递送到损伤动脉中显示出对新生内膜增生的明显抑制。用“模拟物”转染miR-181b到A10细胞后，细胞增殖加速，同时细胞迁移增加。miR-181b诱导A10细胞增殖似乎参与了S和G2/M检查点的激活，同时伴随着细胞周期抑制剂p21和p27的减少，以及细胞周期激活剂CDK4和cyclinD1的增加。相反，miR-181b抑制抑制了A10细胞的增殖，抑制了细胞迁移，阻止了细胞周期转变。此外，强制表达miR-181b会提高Akt和Erk1/2的磷酸化水平，而抑制miR-181b则会产生相反的效果。此外，用特异性抑制剂抑制PI3K和MAPK信号通路，而不抑制JNK通路，可以显著消除miR-181b促进细胞增殖的作用。这些发现表明，miR-181b通过激活PI3K和MAPK途径增强VSMCs的增殖和迁移。
Vascular smooth muscle cells (VSMCs) hyperplasia is a common feature of pathologic cardiovascular event such as restenosis and atherosclerosis. The role and mechanisms of microRNAs (miRs) in VSMCs proliferation are poorly understood. Here, we report that miR-181b promotes VSMCs proliferation and migration. In an animal model, miR-181b was significantly increased in the rat carotid artery after balloon catheter injury. Delivery of miR-181b inhibitor to injured artery exhibited a marked inhibition of neointimal hyperplasia. Transfection of miR-181b with "mimics" to A10 cells accelerated cell proliferation, which was accompanied by an increase of cell migration. The induction of A10 cells proliferation by miR-181b appeared to be involved in activation of S and G2/M checkpoint, concomitant with decreases in cell-cycle inhibitors p21 and p27, and increases in cell-cycle activators CDK4 and cyclinD1. In contract, miR-181b inhibition attenuated A10 cells proliferation, inhibited cell migration and arrested cell cycle transition. Moreover, forced miR-181b expression elevated the phosphorylation levels of Akt and Erk1/2, whereas inhibition of miR-181b produced the opposite effects. Additionally, inhibition of PI3K and MAPK signaling pathways with specific inhibitors, but not inhibition of JNK pathway, significantly abolished the effects of miR-181b in promoting cell proliferation. These findings demonstrate that miR-181b enhances the proliferation and migration of VSMCs through activation of PI3K and MAPK pathways.