首页> 外文期刊>The Journal of Reproduction and Development >IRS2 depletion inhibits cell proliferation and decreases hormone secretion in mouse granulosa cells
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IRS2 depletion inhibits cell proliferation and decreases hormone secretion in mouse granulosa cells

机译:IRS2耗竭抑制小鼠颗粒细胞的细胞增殖并减少激素分泌

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Insulin receptor substrate 2 (IRS2) is a component of the insulin/insulin-like growth factor 1 (IGF1) signaling cascade, which plays an important role in mouse hypothalamic and ovarian functions. The present study was conducted to investigate the role of IRS2 in steroidogenesis, apoptosis, cell cycle and proliferation in mouse granulosa cells (GCs). Flow cytometry and CCK8 assay showed that IRS2 knockdown inhibited cell proliferation, reduced cell viability, and increased apoptosis in GCs. The study also revealed that the expression of Cyclin A1, Cyclin B1 and Bcl2 was downregulated, while the expression of Bax, Cyclin D1 and Cyclin D2 was upregulated. ELISA analysis showed that IRS2 knockdown decreased the concentrations of estradiol (E2) and progesterone (P4), which was further validated by the decreased expression of Star, Cyp11a1, and Cyp19a1. Moreover, IRS2 knockdown altered the expression of Has2 and Ptgs2, which are essential for folliculogenesis. In addition, we found that IRS2-mediated cell viability and hormone secretion are dependent on the PI3K/AKT signaling pathway. Collectively, this study demonstrated that IRS2 plays an important role in the regulation of cell proliferation and steroidogenesis in mouse GCs via the PI3K/AKT signaling pathway.
机译:胰岛素受体底物2(IRS2)是胰岛素/胰岛素样生长因子1(IGF1)信号级联的组成部分,在小鼠下丘脑和卵巢功能中起重要作用。本研究旨在研究IRS2在小鼠颗粒细胞(GCs)的类固醇生成,凋亡,细胞周期和增殖中的作用。流式细胞仪和CCK8分析表明,IRS2抑制可抑制细胞增殖,降低细胞活力并增加GC中的细胞凋亡。研究还显示,Cyclin A1,Cyclin B1和Bcl2的表达下调,而Bax,Cyclin D1和Cyclin D2的表达上调。 ELISA分析表明,IRS2敲低可降低雌二醇(E2)和孕酮(P4)的浓度,这可通过Star,Cyp11a1和Cyp19a1表达的降低进一步证实。此外,IRS2组合式改变了卵泡生成所必需的Has2和Ptgs2的表达。此外,我们发现IRS2介导的细胞生存力和激素分泌取决于PI3K / AKT信号通路。总的来说,这项研究表明IRS2在通过PI3K / AKT信号通路调节小鼠GC中的细胞增殖和类固醇生成中起着重要作用。

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