PI3K/AKT/mTOR通路
蛋白激酶B
细胞凋亡
血管平滑肌
基因敲除
膜联蛋白
生物
癌症研究
流式细胞术
信号转导
标记法
免疫印迹
分子生物学
磷酸化
细胞生长
细胞生物学
下调和上调
内分泌学
基因
生物化学
平滑肌
作者
Lei Wang,Zhengbin Wang,Rui Zhang,Li Huang,Zhikang Zhao,Yi Yang,Likun Cui,Shijie Zhang
出处
期刊:Journal of Cardiovascular Pharmacology
[Ovid Technologies (Wolters Kluwer)]
日期:2021-08-01
卷期号:78 (2): 288-296
被引量:4
标识
DOI:10.1097/fjc.0000000000001051
摘要
Abstract: Vascular smooth muscle cell (VSMC) dysfunction is the main cause of aortic dissection (AD). In this study, we focused on the role and mechanism of miR-4787-5p in regulating VSMC apoptosis. Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of miR-4787-5p in aorta tissues of AD (n = 10) and normal aortic tissues of donors (n = 10). Cell apoptosis was tested by TUNEL assay and Annexin V FITC/PI staining flow cytometry. The expression of PC1 and the PI3K/Akt/FKHR signaling pathway associated proteins in VSMCs was measured by Western blot. We found that the miR-4787-5p was highly expressed in aorta tissues of AD compared with 10 healthy volunteers. Meanwhile, PI3K/Akt/FKHR signaling pathway was inactive in the aortic tissue of AD. The overexpression of miR-4787-5p significantly induced VSMC apoptosis, and miR-4787-5p knockdown showed the opposite results. In addition, polycystic kidney disease 1 gene, which encodes polycystin-1 (PC1), was found to be a direct target of miR-4787-5p in the VSMCs and this was validated using a luciferase reporter assay. Overexpression of PC1 by a lentivirus packaging PC1-overexpression plasmid (LV-PC1) plasmids markedly eliminated the promotion of miR-4787-5p overexpression on VSMC apoptosis. Finally, it was found that miR-4787-5p deactivated the PI3K/Akt/FKHR pathway, as demonstrated by the down-regulation of phosphorylated (p-)PI3K, p-Akt, and p-FKHR. In conclusion, these findings confirm an important role for the miR-4787-5p/polycystic kidney disease 1 axis in AD pathobiology.
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