首页> 外文期刊>Life sciences >Activation of Notch1 signaling by marrow-derived mesenchymal stem cells through cell-cell contact inhibits proliferation of hepatic stellate cells.
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Activation of Notch1 signaling by marrow-derived mesenchymal stem cells through cell-cell contact inhibits proliferation of hepatic stellate cells.

机译:骨髓间充质干细胞通过细胞间接触激活Notch1信号传导可抑制肝星状细胞的增殖。

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AIMS: Bone marrow-derived mesenchymal stem cells (BMSCs) have been reported in many studies to reduce liver fibrosis. Apart from the paracrine mechanism by which the antifibrotic effects of BMSCs inhibit activated hepatic stellate cells (HSCs), the effects of direct interplay and juxtacrine signaling between the two cell types are poorly understood. The purpose of this study was to explore the underlying mechanisms by which BMSCs modulate the function of activated HSCs. MAIN METHODS: We show here that BMSCs directly cocultured with HSCs significantly suppressed the proliferation and alpha-smooth muscle actin (alpha-SMA) expression of HSCs. Moreover, the Notch1 and Hes1 mRNA levels and the Hes1 protein level in cocultured HSCs were evidently higher than in other models. Blocking the Notch signaling pathway with Notch1 siRNA caused the increased expression of phospho-Akt and greater cell growth of cocultured HSCs. This effect was attenuated by the PI3K inhibitor LY294002. KEY FINDINGS: In conclusion, our results demonstrated that BMSCs remarkably inhibited the proliferation of HSCs through a cell-cell contact mode that was partially mediated by Notch pathway activation. In addition, the PI3K/Akt pathway is involved in HSC growth inhibition by the Notch pathway. SIGNIFICANCE: These findings demonstrated that BMSCs directly modulate HSCs in vitro via Notch signaling cascades. Our results may provide new insights into the treatment of hepatic fibrosis with BMSCs.
机译:目的:在许多研究中已报道了骨髓来源的间充质干细胞(BMSCs)可减少肝纤维化。除了通过旁分泌机制抑制BMSC的抗纤维化作用抑制活化的肝星状细胞(HSC)以外,对两种细胞类型之间的直接相互作用和邻分泌的信号传导的作用还知之甚少。本研究的目的是探讨BMSC调节激活的HSC功能的潜在机制。主要方法:我们在这里显示,与HSC直接共培养的BMSC可以显着抑制HSC的增殖和α-平滑肌肌动蛋白(alpha-SMA)表达。此外,在共培养的HSC中,Notch1和Hes1 mRNA水平以及Hes1蛋白水平明显高于其他模型。用Notch1 siRNA阻断Notch信号通路会导致磷酸化Akt的表达增加以及共培养的HSC的更大细胞生长。 PI3K抑制剂LY294002减弱了该作用。关键发现:总之,我们的结果表明BMSC通过Notch途径活化部分介导的细胞间接触模式显着抑制了HSC的增殖。另外,PI3K / Akt途径通过Notch途径参与HSC生长抑制。意义:这些发现表明,BMSC通过Notch信号级联反应在体外直接调节HSC。我们的结果可能为BMSCs治疗肝纤维化提供新的见解。

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