sh- Ambra1抑制IRS-1/PI3K/Akt信号通路,减少妊娠糖尿病患者的自噬。

Xin Qu, Xiao-Yan Li, Yan Feng, Xiaoli Wang, Lei Li, Yu-Ping Wang, Yong-Li Chu
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引用次数: 0

摘要

导言妊娠糖尿病(GDM)是妊娠期最常见的代谢性疾病。然而,有关贝克林1调节自噬激活分子(Ambra1)影响胰岛素底物受体1/磷脂酰肌醇3激酶/蛋白激酶B(IRS-1/PI3K/Akt)信号通路在GDM中的作用的研究尚未见报道。本研究旨在检测正常孕妇和 GDM 患者胎盘中 Ambra1 表达的差异:材料和方法:通过高糖诱导人绒毛滋养层的 HTR8/Svneo 细胞,建立了妊娠糖尿病的体外模型。用倒置显微镜观察细胞形态的变化,并检测模型细胞中 Ambra1 基因和蛋白的表达水平。之后,通过 shRNA 转染沉默 Ambra1 基因,并加入 PI3K 抑制剂检测 Ambra1、自噬和胰岛素(INS)信号通路的变化:结果:GDM孕妇胎盘中Ambra1、Bcl-2相互作用蛋白(Beclin-1)和微管相关蛋白1A/1B轻链3B(LC3-II)的蛋白表达水平高于正常孕妇。sh-Ambra1 提高了 HTR8/SvNEO-HG 细胞的存活率,抑制了 Ambra1、Beclin1 和 LC3-II 的转录和翻译水平。此外,sh-Ambra1 还提高了 IRS-1/PI3K/Akt 蛋白的磷酸化水平,抑制了 IRS-1/PI3K/Akt 信号通路及其导致的自噬。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
sh- Ambra1 inhibits IRS-1/PI3K/Akt signalling pathway to reduce autophagy in gestational diabetes.

Introduction: Gestational diabetes mellitus (GDM) is the most common metabolic disease in pregnancy. However, studies of activating molecule of Beclin1-regulated autophagy (Ambra1) affecting the insulin substrate receptor 1/phosphatidylinositol 3 kinase/protein kinase B (IRS-1/PI3K/Akt) signalling pathway in GDM have not been reported. The aim of the study was to detect the difference of Ambra1 expression in the placenta of normal pregnant women and GDM patients.

Material and methods: An in vitro model of gestational diabetes mellitus was established by inducing HTR8/Svneo cells from human chorionic trophoblast layer with high glucose. The changes of cell morphology were observed by inverted microscope, and the expression levels of Ambra1 gene and protein in model cells were detected. After this, Ambra1 gene was silenced by shRNA transfection, and PI3K inhibitor was added to detect changes in Ambra1, autophagy, and insulin (INS) signalling pathways.

Results: The protein expression levels of Ambra1, Bcl-2 interacting protein (Beclin-1), and microtubule-associated proteins 1A/1B light chain 3B (LC3-II) in the placentas of GDM pregnant women were higher than those of normal pregnant women. High glucose induces morphological changes in HTR8/Svneo cells and increases Ambra1 transcription and translation levels. sh-Ambra1 increased survival of HTR8/SvNEO-HG cells and inhibited Ambra1, Beclin1, and LC3-II transcription and translation levels. Also, sh-Ambra1 increased IRS-1/PI3K/Akt protein phosphorylation levels and inhibited the IRS-1/PI3K/Akt signalling pathway and its resulting autophagy.

Conclusions: sh-Ambra1 increased IRS-1/PI3K/Akt protein phosphorylation levels to reduce autophagy in gestational diabetes.

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