MiR-182-5p Inhibits the Proliferation of Vascular Smooth Muscle Cells Induced by ox-LDL Through Targeting PAPPA

被引:22
作者
Jin, Chaolong [1 ]
Gao, Shan [2 ]
Li, Dayuan [1 ]
Shi, Xuegong [1 ]
Hu, Zhangyue [3 ]
Wang, Chunmiao [4 ]
Xiao, Jie [1 ]
Sheng, Zhe [1 ]
Ding, Zhifeng [1 ]
Zhang, Dingxin [1 ]
Wang, Di [1 ]
Wang, Tingting [1 ]
Yang, Fang [1 ]
Yang, Ying [1 ]
Wang, Xinglong [1 ]
Wu, Liping [1 ]
Xu, Yue [1 ]
机构
[1] Anhui Med Univ, Affiliated Hosp 1, Heart Ctr, Dept Cardiovasc Color Doppler, Hefei, Peoples R China
[2] Anhui Med Univ, Dept Pharmacol, Basic Med Coll, 69 Meishan Rd, Hefei 230022, Anhui, Peoples R China
[3] Anhui Med Univ, Affiliated Hosp 2, Dept Cardiol, Hefei, Peoples R China
[4] Anhui Med Univ, Affiliated Hosp 1, Heart Ctr, Dept Cardiol, Hefei, Peoples R China
基金
中国国家自然科学基金;
关键词
miRNAs; Atherosclerosis; RNA interference; Signaling pathway; qRT-PCR; PLASMA PROTEIN-A; APOPTOSIS; GROWTH; ATHEROSCLEROSIS; MIGRATION; INFLAMMATION; MICRORNAS; DISEASE; IGF;
D O I
10.1536/ihj.19-708
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
This study aims to analyze the expression level and correlation of miR-182-5p and its target gene PAPPA in coronary atherosclerosis (CAD). Real time PCR, ELISA, and Western blotting methods were used to detect the expression levels. Dual-luciferase reporter gene assays were used to analyze the interaction between the 3'-UTR of PAPPA and miR-182-5p. The expression level of miR-182-5p in CAD was significantly lower than that in normal population, while the content of serum PAPPA was significantly increased, and the expression level of miR-182-5p was negatively correlated with the PAPPA content. The expression level of miR-182-5p decreased, while the expression level of PAPPA increased significantly in the ox-LDL treated HA-VSMC cells. Researchers found that PAPPA could promote the activation of IGF signaling pathway in HA-VSMC cells treated by ox-LDL, further activate NFkB, PI3K/AKT and ERK signaling pathway, and promote cell proliferation. However, miR-182-5p could inhibit the expression of PAPPA, block the activation of IGF signal pathway, and inhibit the proliferation of HA-VSMC cells induced by ox-LDL. miR-182-5p had a targeted action site in the 3'-UTR of PAPPA by bioinformatics prediction. The analysis of luciferase reporter gene further confirmed that miR-182-5p could target the 3'-UTR of PAPPA to inhibit its expression. miR-182-5p demonstrated a protective effect on atherosclerosis and may be a potential therapeutic target for atherosclerosis.
引用
收藏
页码:822 / 830
页数:9
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