miR-21 regulates vascular smooth muscle cell function in arteriosclerosis obliterans of lower extremities through AKT and ERK1/2 pathways

被引:17
作者
Huang, Shuichuan [1 ]
Xu, Tuo [2 ]
Xianying Huang [1 ]
Li, Siyi [2 ]
Qin, Wenyi [2 ]
Chen, Weijie [2 ]
Zhang, Zhi [2 ]
机构
[1] Southern Med Univ, Nanfang Hosp, Dept Vasc Surg, Guangzhou, Guangdong, Peoples R China
[2] Guangdong Med Univ, Affiliated Hosp, Dept Vasc Surg, 57 South Renmindadao, Zhanjiang 524001, Guangdong, Peoples R China
关键词
arteriosclerosis obliterans; miR-21; HASMCs; AKT; ERK; PERIPHERAL ARTERIAL-DISEASE; ATHEROSCLEROSIS; PROLIFERATION; EXPRESSION; MIGRATION; KINASE;
D O I
10.5114/aoms.2018.78885
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Introduction: Arteriosclerosis obliterans (ASO) is a disease that affects the lower extremities. The mechanism of ASO is associated with the proliferation and migration of vascular smooth muscle cells (VSMCs). miR-21 plays a key role in various biological processes of the cardiovascular system, associated with the proliferation, migration and apoptosis of VSMCs. It is unclear, however, if miR-21 is involved in the regulation of ASO. Material and methods: Human aortic smooth muscle cells (HASMCs) were transfected with miR-21 mimics and co-treated with protein kinase B (AKT) or a mitogen-activated protein kinase (ERK) inhibitor. Expression levels of p-AKT or p-ERK were measured by western blot. Cell apoptosis was assessed using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and visualized under a fluorescence microscope. Cell proliferation was monitored by bromodeoxyuridine (BrdU) labeling; cell migration and invasion were determined by the Transwell assay. Results: miR-21 was upregulated in arteries of ASO, the pathogenesis of which involved the activation of p-AKT and p-ERK1/2. Inhibition of the AKT or ERK activity was consistent with the attenuation of the miR-21-induced HASMC migration and proliferation. HASMCs co-treated with miR-21 mimics and AKT or ERK inhibitor showed attenuation of the miR-21-induced high elongation ratio. Conclusions: We demonstrated that the expression of miR-21 in HASMCs could find potential application in cardiac therapy. Inhibition of the activity of AKT or ERK could attenuate miR-21-induced cell proliferation and migration as well as altering morphology of HASMCs. The present study aimed to indicate the potential roles of miR-21 in ASO processes, and the results provided a novel therapeutic approach for treating ASO and new targets for preventing ASO in earlier stages.
引用
收藏
页码:1490 / 1497
页数:8
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