MicroRNA-183对急性主动脉夹层细胞外基质重塑的作用及其机制研究

The role of microRNA-183 in regulating extracellular matrix remodeling in the setting of acute aortic dissection and its mechanism

摘要:

目的 探讨microRNA-183（miR-183）和基质金属蛋白酶-9（MMP-9）在急性主动脉夹层（AAD）中的表达水平及其参与调节平滑肌细胞细胞外基质（ECM）的机制。方法 收集20例确诊为AAD的组织标本作为AAD组，20例无主动脉病变的冠状动脉粥样硬化性心脏病患者的组织标本作为NC组，采用实时荧光定量聚合酶链反应（qRT-PCR）和Western blotting检测检测miR-183、MMP-9蛋白相对表达量。将人主动脉平滑肌细胞（HASMC）分为3组：Mimic组、Inhibitor组和对照组；Mimic组用miRNA-183 mimic转染HASMC；Inhibitor组用miRNA-183 inhibitor转染HASMC，对照组未做处理。采用qRT-PCR和Western blotting检测miR-183、MMP-9 mRNA、MMP-9蛋白及其底物弹性蛋白（Elastin）的表达。结果 AAD组miRNA-183相对表达量低于NC组（P <0.05），而MMP-9蛋白相对表达量高于NC组（P <0.05）。与对照组比较，Mimic组miRNA-183、Elastin升高（P <0.05），MMP-9 mRNA和蛋白降低（P <0.05）；Inhibitor组miRNA-183、Elastin降低（P <0.05），MMP-9 mRNA和蛋白升高（P <0.05）。结论 miR-183可能通过调控平滑肌细胞中MMP-9的表达，参与平滑肌细胞ECM的重塑过程，促进AAD的发生、发展。

Abstract:

Objective To explore the expressions of microRNA-183 and matrix metalloproteinase-9 (MMP-9) in acute aortic dissection (AAD) and the mechanisms underlying their regulation of extracellular matrix of smooth muscle cells.Methods The tissue samples of 20 patients with AAD and 20 patients with coronary heart disease without the involvement of aorta were collected and set as AAD group and NC group, respectively. The relative expressions of miR-183 and MMP-9 in these samples were detected. The human aortic smooth muscle cells (HASMC) were divided into mimic group, inhibitor group and control group, where the cells were transfected with miRNA-183 mimics, miRNA-183 inhibitors or untreated. The expressions of miRNA-183, MMP-9 mRNA, MMP-9 protein, and its substrate elastin were detected.Results The relative expression of miRNA-183 in AAD group was lower than that in NC group (P < 0.05), while the relative expression of MMP-9 protein in AAD group was higher than that in NC group (P < 0.05). Compared with the control group, the expressions of microRNA-183 and elastin were increased, but the mRNA and protein expressions of MMP-9 were decreased in mimic group (P < 0.05). In contrast, the expressions of microRNA-183 and elastin were decreased, but the mRNA and protein expressions of MMP-9 were increased in inhibitor group relative to those in control group (P < 0.05).Conclusions MicroRNA-183 may participate in the extracellular matrix remodeling by regulating the expression of MMP-9 in smooth muscle cells, thereby promoting the development of acute aortic dissection.