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miR-126 对 PI3K/AKT/mTOR 信号通路下调对腹主动脉瘤小鼠血管平滑肌细胞增殖和迁移的影响。

Effect of miR-126 on the Proliferation and Migration of Vascular Smooth Muscle Cells in Aortic Aneurysm Mice Under PI3K/AKT/mTOR Signaling Pathway.

机构信息

Department of Vascular Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, Zhejiang Province, China.

出版信息

Mol Biotechnol. 2021 Jul;63(7):631-637. doi: 10.1007/s12033-021-00327-6. Epub 2021 May 10.

Abstract

This paper is to investigate the expression changes of Phosphatidylinositol-3 Kinase (PI3K), protein kinase B (AKT), and Mammalian Target of Rapamycin (mTOR) in Vascular Smooth Muscle Cells (VSMCs) of aortic aneurysm mice, and to analyze the mechanism of VSMCs proliferation and migration. Aortic VSMCs cells were cultured using BALB/c mice as the research object. VSMCs were identified using artificial intelligence-based digital microscopy equipment, and liposome-transfected VSMCs experiments were performed. Real-time PCR was used for the mRNA expression levels of miR-126 and Phosphatase and Tensin Homolog (PTEN). Western blot was used for the protein expression levels of PTEN, PI3K, AKT, and mTOR. The cultured cells were identified as mouse VSMCs using digital microscopes based on artificial intelligence. Compared with the normal group, the expression of miR-126 and PTEN mRNA in the model group were significantly increased and reduced, respectively. Compared with the model group, the expression level of miR-126 and PTEN mRNA in the inhibitor group were significantly reduced and increased, respectively. Compared with the model group, the expression of miR-126 and PTEN mRNA in the ursolic acid group was significantly reduced and increased, respectively. After liposome transfection, compared with the normal group, the expression of PTEN protein in the model group was significantly reduced, and the expression of PI3K protein was significantly increased. Compared with the model group, the expression of PTEN protein was significantly increased and the expression of PI3K protein was significantly decreased in the transfection group. Compared with the control group, the expression of PI3K, AKT and mTOR protein in the model group was significantly increased. Compared with the model group, the expression of PI3K, AKT, and mTOR protein in the ursolic acid group was significantly reduced. The expressions of PI3K, AKT and mTOR protein in PI3K inhibitor group and AKT inhibitor group were significantly reduced. In conclusion, ursolic acid can inhibit the proliferation and migration of VSMCs in aortic aneurysm mice through the miR-126/PTEN/PI3K/AKT/mTOR signaling pathway. Furthermore, PTEN gene and miR-126 negatively regulate PI3K/AKT/mTOR and PTEN/PI3K/AKT/mTOR signaling pathway, respectively .

摘要

本文旨在研究磷脂酰肌醇-3 激酶(PI3K)、蛋白激酶 B(AKT)和雷帕霉素靶蛋白(mTOR)在主动脉瘤小鼠血管平滑肌细胞(VSMCs)中的表达变化,并分析 VSMCs 增殖和迁移的机制。以 BALB/c 小鼠为研究对象,采用组织块贴壁法培养主动脉 VSMCs。利用基于人工智能的数字显微镜设备鉴定 VSMCs,进行脂质体转染 VSMCs 实验。实时 PCR 检测 miR-126 和磷酸酶和张力蛋白同源物(PTEN)的 mRNA 表达水平。Western blot 检测 PTEN、PI3K、AKT 和 mTOR 的蛋白表达水平。利用基于人工智能的数字显微镜鉴定培养的细胞为小鼠 VSMCs。与正常组相比,模型组 miR-126 和 PTEN mRNA 的表达明显增加和减少。与模型组相比,抑制剂组 miR-126 和 PTEN mRNA 的表达水平明显降低和增加。与模型组相比,熊果酸组 miR-126 和 PTEN mRNA 的表达明显降低和增加。转染脂质体后,与正常组相比,模型组 PTEN 蛋白表达明显减少,PI3K 蛋白表达明显增加。与模型组相比,转染组 PTEN 蛋白表达明显增加,PI3K 蛋白表达明显减少。与对照组相比,模型组 PI3K、AKT 和 mTOR 蛋白表达明显增加。与模型组相比,熊果酸组 PI3K、AKT 和 mTOR 蛋白表达明显减少。PI3K 抑制剂组和 AKT 抑制剂组的 PI3K、AKT 和 mTOR 蛋白表达明显减少。综上所述,熊果酸通过 miR-126/PTEN/PI3K/AKT/mTOR 信号通路抑制主动脉瘤小鼠 VSMCs 的增殖和迁移。此外,PTEN 基因和 miR-126 分别负调控 PI3K/AKT/mTOR 和 PTEN/PI3K/AKT/mTOR 信号通路。

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