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首页> 外文期刊>Vascular pharmacology >Gleditsioside B, a triterpene saponin isolated from the anomalous fruits of Gleditsia sinensis Lam., abrogates bFGF-induced endothelial cell migration through preventing the activation of MMP-2 and FAK via inhibiting ERK and PI3K/AKT signaling pathways
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Gleditsioside B, a triterpene saponin isolated from the anomalous fruits of Gleditsia sinensis Lam., abrogates bFGF-induced endothelial cell migration through preventing the activation of MMP-2 and FAK via inhibiting ERK and PI3K/AKT signaling pathways

机译:从皂角异常果实中分离出的三萜皂苷皂角甙B通过抑制ERK和PI3K / AKT信号通路来阻止MMP-2和FAK的活化,从而消除了bFGF诱导的内皮细胞迁移。

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摘要

Angiogenesis has become an attractive target for the treatment of certain diseases such as cancer and rheumatoid arthritis. Our previous studies demonstrated that the saponin fraction from Gleditsia sinensis fruits had anti-angiogenic potential, and Gleditsiosides B (GB) was probably the main active constituent. In the present study, we assessed the effect of GB on endothelial cell migration, a crucial event in angiogenesis, and explored the underlying mechanisms. The migration of endothelial cells was assessed by transwell. The expressions of MMP-2/-9 and TIMP-1/-2 were analyzed by Western blotting, and the activities of MMP-2/-9 were detected by gelatin zymography assay. Moreover, migration-related proteins and signaling pathways, including FAK, MAPKs and PI3K/AKT, were analyzed by Western blotting. It was shown that GB, at a concentration of 10. μM without significant cytotoxicity, could effectively abrogate the migration of human umbilical vein endothelial cells (HUVECs) induced by bFGF. GB also inhibited the expression and activity of MMP-2, elevated the expression of TIMP-1, and restrained the phosphorylations of FAK, ERK, PI3K and AKT in a concentration-dependent manner. The findings suggest that GB was able to abrogate the migration of endothelial cells through down-regulating the activation of MMP-2 and FAK via preventing ERK and PI3K/AKT signaling pathways.
机译:血管生成已成为治疗某些疾病如癌症和类风湿关节炎的有吸引力的靶标。我们以前的研究表明,皂角果实中的皂苷成分具有抗血管生成的潜力,而皂角甙B(GB)可能是主要的活性成分。在本研究中,我们评估了GB对内皮细胞迁移(血管生成中的关键事件)的影响,并探讨了其潜在机制。通过transwell评估内皮细胞的迁移。用蛋白质印迹法分析MMP-2 / -9和TIMP-1 / -2的表达,并用明胶酶谱法检测MMP-2 / -9的活性。此外,通过蛋白质印迹分析了与迁移相关的蛋白质和信号传导途径,包括FAK,MAPK和PI3K / AKT。结果表明,浓度为10μM的GB没有明显的细胞毒性,可以有效消除bFGF诱导的人脐静脉内皮细胞(HUVEC)迁移。 GB还以浓度依赖的方式抑制MMP-2的表达和活性,提高TIMP-1的表达,并抑制FAK,ERK,PI3K和AKT的磷酸化。研究结果表明,GB通过阻止ERK和PI3K / AKT信号传导通路,通过下调MMP-2和FAK的活化,从而消除了内皮细胞的迁移。

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